From: Transgenic rat models for mutagenesis and carcinogenesis
Agents | Animal | Dose | Route | Sex | Age (weeks) | Administration time/Sampling time (days) | Tissue | Transgenic assays | Positive response | Reference |
---|---|---|---|---|---|---|---|---|---|---|
Acetaminophen | gpt delta rat (SD) | 10000Â ppm | Diet | Female | 11 | 91/91 | Liver | gpt | - | [167] |
Acrylamide | Big Blue rat (F344) | 1.4Â mM | Drinking water | Male | 7 | 60/60 | Liver | cII | - | [168] |
Bone marrow | cII | - | Ibid | |||||||
Thyroid | cII | - | Ibid | |||||||
Testis | cII | Â | Ibid | |||||||
gpt delta rat (F344) | 0.7Â mM | Drinking water | Female | 7 | 60/60 | Liver | cII | - | Ibid | |
Bone marrow | cII | + | Ibid | |||||||
Thyroid | cII | + | ibid | |||||||
Mammary gland | cII | - | Ibid | |||||||
Male | 7 | 60/60 | Liver | cII | - | Ibid | ||||
Female | 7 | 60/60 | Liver | cII | - | Ibid | ||||
80Â ppm | Drinking water | Male | 3 | 28/28 | Testis | gpt | + | [169] | ||
Liver | gpt | - | Ibid | |||||||
40Â ppm | Testis | gpt | - | Ibid | ||||||
Liver | gpt | - | Ibid | |||||||
20Â ppm | Testis | gpt | - | Ibid | ||||||
Liver | gpt | - | Ibid | |||||||
80Â ppm | Drinking water | Male | 11 | 28/28 | Testis | gpt | - | Ibid | ||
Liver | gpt | - | Ibid | |||||||
40Â ppm | Testis | gpt | - | Ibid | ||||||
20Â ppm | Liver | gpt | - | Ibid | ||||||
Testis | gpt | - | Ibid | |||||||
Liver | gpt | - | ibid | |||||||
Aflatoxin B1 | Big Blue rat (F344) | 0.5Â mg/kg | Gavage | Male | 13 | 1/14 | Liver | lacI | + | [105] |
Female | 13 | 1/14 | Liver | lacI | + | Ibid | ||||
0.5 mg/kg | Gavage | Female | 6–8 | 1/14 | Liver | lacI | + | [170] | ||
cII | + | [109] | ||||||||
0.25 mg/kg | Intraperitoneal | Male | 13–19 | 1/14 | Liver | lacI | + | [18] | ||
2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) | Big Blue rat (F344) | 20Â mg.kg | Gavage | Male | 5 | 1/14 | Liver | lacI | + | [171] |
Colon | lacI | + | Ibid | |||||||
Kidney | lacI | + | Ibid | |||||||
20Â mg/kg x5 | Gavage | Male | 5 | 5/18 | Liver | lacI | + | Ibid | ||
Colon | lacI | + | Ibid | |||||||
Kidney | lacI | + | Ibid | |||||||
200Â ppm | Diet | Male | 8 | 21/21 | Liver | cII | + | [172] | ||
Colon | cII | + | Ibid | |||||||
70Â ppm | Diet | Male | 8 | 21/21 | Liver | cII | + | Ibid | ||
Colon | cII | + | Ibid | |||||||
9–12 | 21/21 | Liver | cII | + | [100] | |||||
Colon | cII | + | Ibid | |||||||
20Â ppm | Diet | Male | 8 | 21/21 | Liver | cII | - | [172] | ||
Colon | cII | - | Ibid | |||||||
gpt delta rat (SD) | 300Â ppm | Diet | Female | 11 | 91/91 | Liver | gpt | + | [167] | |
2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) | Big Blue rat (F344) | 100Â ppm | Diet | Male | 6 | 112/112 | Liver | lacI | + | [85] |
Colon | lacI | + | Ibid | |||||||
Zymbal gland | lacI | + | Ibid | |||||||
Kidney | lacI | - | Ibid | |||||||
Spleen | lacI | - | Ibid | |||||||
Lung | lacI | - | Ibid | |||||||
Testis | lacI | - | Ibid | |||||||
Heart | lacI | - | Ibid | |||||||
Brain | lacI | - | Ibid | |||||||
Fat tissue | lacI | - | Ibid | |||||||
Skeletal muscle | lacI | - | Ibid | |||||||
10Â ppm | Diet | Male | 6 | 112/112 | Liver | lacI | + | Ibid | ||
1Â ppm | Diet | Male | 6 | 112/112 | Liver | lacI | - | Ibid | ||
0.1Â ppm | Diet | Male | 6 | 112/112 | Liver | lacI | - | Ibid | ||
0.01Â ppm | Diet | Male | 6 | 112/112 | Liver | lacI | - | Ibid | ||
0.001Â ppm | Diet | Male | 6 | 112/112 | Liver | lacI | - | Ibid | ||
2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) | Big Blue rat (F344) | 100Â mg/kg, bw | Intraperitoneal | Male | 8+22 | 1/14 | Colon | lacI | + | [102] |
Female | 8+22 | 1/14 | Colon | lacI | + | Ibid | ||||
75 mg/kg ×10 | Oral | Female | 7 | 12/54 | Mammary gland | lacI | + | [40] | ||
22 | 12/54 | Mammary gland | lacI | + | Ibid | |||||
70 mg/kg ×12 | Gavage | Male | 13–15 | 28/30 | Liver | cII | - | [41] | ||
Kidney | cII | - | Ibid | |||||||
Prostate | cII | + | Ibid | |||||||
Seminal vesicle | cII | + | Ibid | |||||||
Colon | cII | + | Ibid | |||||||
Spleen | cII | + | Ibid | |||||||
70 mg/kg ×24 | Gavage | Male | 13–15 | 56/60 | Liver | cII | - | Ibid | ||
Kidney | cII | - | Ibid | |||||||
Prostate | cII | + | Ibid | |||||||
Seminal vesicle | cII | + | Ibid | |||||||
Colon | cII | + | Ibid | |||||||
Spleen | cII | + | Ibid | |||||||
400Â ppm | Diet | Male | 6 | 60/67 | Colon mucosa | lacI | + | |||
cII | + | [23] | ||||||||
Female | 6 | 60/67 | Colon mucosa | lacI | + | |||||
cII | + | [23] | ||||||||
200Â ppm | Diet | Male | 7 | 61/68 | Distal colon | lacI | + | |||
Proximal colon | lacI | + | Ibid | |||||||
Cecum | lacI | + | Ibid | |||||||
Prostate | lacI | + | [42] | |||||||
Female | 7 | 61/68 | Distal colon | lacI | + | [45] | ||||
Proximal colon | lacI | + | Ibid | |||||||
Cecum | lacI | + | Ibid | |||||||
100Â ppm | Diet | Male and Female | 7 | 47/54 | Distal colon | lacI | + | [174] | ||
Cecum | lacI | + | Ibid | |||||||
Male | 7 | 47/54 | Kidney | lacI | + | [98] | ||||
Female | 7 | 47/54 | Kidney | lacI | + | Ibid | ||||
Big Blue rat (F344 × SD)F1 | 65 mg/kg ×10 | Gavage | Female | 6 | 12/350–441 | Mammary gland | lacI | + | [39] | |
Amosite asbestos | Big Blue rat (F344) | 2Â mg/rat | Intratracheal | Male | 11 | 1/28 | Lung | lacI | - | |
1/112 | Lung | lacI | + | Ibid | ||||||
2 mg/rat ×4 | Intratracheal | Male | 11 | 28/56 | Lung | lacI | - | Ibid | ||
28/133 | Lung | lacI | + | Ibid | ||||||
1Â mg/rat | Intratracheal | Male | 11 | 1/28 | Lung | lacI | - | Ibid | ||
1/112 | Lung | lacI | - | Ibid | ||||||
Aristolochic acid | Big Blue rat (F344) | 10Â mg/kg | Gavage | Male | 6 | 84/84 | Kidney | cII | + | |
Liver | cII | + | [112] | |||||||
Testis | cII | - | [175] | |||||||
1.0Â mg/kg | Gavage | Male | 6 | 84/84 | Kidney | cII | + | |||
Liver | cII | + | [112] | |||||||
0.1Â mg/kg | Gavage | Male | 6 | 84/84 | Kidney | cII | + | |||
Liver | cII | - | [112] | |||||||
Big Blue rat (F344) | 10Â mg/kg | Gavage | Male | 6 | 84/84 | Spleen | cII | + | [176] | |
1.0Â mg/kg | Gavage | 6 | 84/84 | Spleen | cII | + | Ibid | |||
0.1Â mg/kg | Gavage | 6 | 84/84 | Spleen | cII | - | Ibid | |||
gpt delta rat (F344) | 1Â mg/kg | Gavage | Male | 7 | 28/31 | Kidney | gpt | + | [177] | |
0.3Â mg/kg | Gavage | 7 | 28/31 | Liver | gpt | + | Ibid | |||
Benzo[a]pyrene (BP) | Big Blue rat (F344) | 100Â mg/kg, bw | Intraperitoneal | Male | 8+22 | 1/14 | Liver | lacI | + | [102] |
Female | 8+22 | 1/14 | Liver | lacI | + | Ibid | ||||
5Â mg/rat | Intraperitoneal | Female | 10 | 1/28 | Omentum | lacI | + | [178] | ||
1/84 | Omentum | lacI | + | Ibid | ||||||
1/168 | Omentum | lacI | + | Ibid | ||||||
gpt delta rat (SD) | 125 mg/kg | Intraperitoneal | Male | 9–10 | 1/7 | Liver | gpt | + | [17] | |
Spi– | + | Ibid | ||||||||
62.5 mg/kg | Intraperitoneal | Male | 9–10 | 1/7 | Liver | gpt | + | Ibid | ||
Spi− | - | Ibid | ||||||||
Bitumen fumes | Big Blue rat (F344) | 6 hr ×5 | Inhalation | Male | 8 | 5/35 | Lung | cII | - | [132] |
 | Ibid | |||||||||
N-butyl-N-(4-hydroxybutyl)nitrosamine | Big Blue rat (F344) | 0.05Â % | Drinking water | Male | 8 | 14/42 | urothelial cells (urinary bladder) | cII | + | [179] |
smooth muscle cells (urinary bladder) | cII | - | Ibid | |||||||
Ureter | cII | - | Ibid | |||||||
Kidney | cII | - | Ibid | |||||||
Liver | cII | - | Ibid | |||||||
42/70 | urothelial cells (urinary bladder) | cII | + | Ibid | ||||||
smooth muscle cells (urinary bladder) | cII | + | Ibid | |||||||
Ureter | cII | - | Ibid | |||||||
Kidney | cII | - | Ibid | |||||||
Liver | cII | - | Ibid | |||||||
Citrinin | gpt delta rat (F344) | 40Â mg/kg (decreased to 30Â mg/kg at day 4) | Gavage | Male | Â | 28/31 | Kidney | gpt | - | [65] |
20Â mg/kg | 28/31 | Kidney | gpt | - | Ibid | |||||
Comfrey | Big Blue rat (F344) | 2Â % | Diet | Male | 6 | 84/84 | Liver | cII | + | [180] |
Conjugated linoleic acid | Big Blue rat (F344) | 1Â %(w/w) | Diet | Male and Female | 7 | 54/61 | Distal colon | lacI | - | [174] |
Cecum | lacI | - | Ibid | |||||||
Kidney | lacI | - | [98] | |||||||
Crocidolite | Big Blue rat (F344) | 5Â mg/rat | Intraperitoneal | Female | 10 | 1/28 | Omentum | lacI | - | [178] |
1/84 | Omentum | lacI | + | Ibid | ||||||
1/168 | Omentum | lacI | + | Ibid | ||||||
2Â mg/rat | Intraperitoneal | Female | 10 | 1/28 | Omentum | lacI | - | Ibid | ||
1/84 | Omentum | lacI | - | Ibid | ||||||
1/168 | Omentum | lacI | - | Ibid | ||||||
Cyproterone acetate | Big Blue rat (F344) | 160Â mg/kg | Gavage | Female | 12 | 1/14 | Liver | lacI | + | [90] |
100Â mg/kg | Gavage | Female | 12 | 1/1 | Liver | lacI | + | Ibid | ||
1/2 | Liver | lacI | + | Ibid | ||||||
1/3 | Liver | lacI | + | Ibid | ||||||
1/7 | Liver | lacI | + | Ibid | ||||||
1/14 | Liver | lacI | + | Ibid | ||||||
1/28 | Liver | lacI | + | Ibid | ||||||
1/42 | Liver | lacI | + | Ibid | ||||||
1/56 | Liver | lacI | + | Ibid | ||||||
80Â mg/kg | Gavage | Female | 12 | 1/14 | Liver | lacI | + | Ibid | ||
40Â mg/kg | Gavage | Female | 12 | 1/14 | Liver | lacI | + | Ibid | ||
20Â mg/kg | Gavage | Female | 12 | 1/14 | Liver | lacI | + | Ibid | ||
10Â mg/kg | Gavage | Female | 12 | 1/14 | Liver | lacI | + | Ibid | ||
5Â mg/kg | Gavage | Female | 12 | 1/14 | Liver | lacI | - | Ibid | ||
5 mg/kg ×21 | Gavage | Female | 11–12 | 21/22 | Liver | lacI | + | [181] | ||
1.0 mg/kg ×21 | Gavage | Female | 11–12 | 21/22 | Liver | lacI | - | Ibid | ||
0.2 mg/kg ×21 | Gavage | Female | 11–12 | 21/22 | Liver | lacI | - | Ibid | ||
Daidzein | Big Blue rat (F344) | 1Â g/kg | Diet | Female | 7 | 112/112 | Mammary gland | lacI | - | [95] |
Uterus | lacI | - | [96] | |||||||
0.25Â g/kg | Diet | Female | 7 | 112/112 | Mammary gland | lacI | - | [95] | ||
Uterus | lacI | - | [96] | |||||||
Big Blue rat (F344), ovariectomized | 1Â g/kg | Diet | Female | 7 | 112/112 | Uterus | lacI | - | [96] | |
0.25Â g/kg | Diet | Female | 7 | 112/112 | Uterus | lacI | - | Ibid | ||
Diallyl sulfide (DAS) | Big Blue rat (F344) | 200 mg/kg ×2 | Gavage | Male | 7–10 | 7/21 | Esophagus | lacI | - | [93] |
2,4-diaminotoluene (2,4-DAT) | gpt delta rat (F344) | 30Â mg/kg | Gavage | Male | 7 | 28/31 | Liver | gpt | + | [55] |
10Â mg/kg | Gavage | Male | 7 | 28/31 | Liver | gpt | + | Ibid | ||
gpt delta rat (F344) | 500 ppm | Diet | Male | 7 | 91/91 | Liver | gpt, Spi− | + | [7] | |
500Â ppm | Diet | Male | 7 | 91/91 | Kidney | gpt | - | Ibid | ||
250 ppm | Diet | Male | 7 | 91/91 | Liver | gpt, Spi− | + | Ibid | ||
250Â ppm | Diet | Male | 7 | 91/91 | Kidney | gpt | - | Ibid | ||
125Â ppm | Diet | Male | 7 | 91/91 | Liver | gpt | + | Ibid | ||
125Â ppm | Diet | Male | 7 | 91/91 | Liver | Spi- | - | Ibid | ||
125Â ppm | Diet | Male | 7 | 91/91 | Kidney | gpt | - | Ibid | ||
2,6-diaminotoluene (2.6-DAT) | gpt delta rat (F344) | 60Â mg/kg | Gavage | Male | 7 | 28/31 | Liver | gpt | - | [55] |
gpt delta rat (F344) | 500 ppm | Diet | Male | 7 | 91/91 | Liver | gpt, Spi− | - | [7] | |
500Â ppm | Diet | Male | 7 | 91/91 | kideny | gpt | - | Ibid | ||
1,2,3,4-Diepoxybutane | Big Blue rat (F344) | 3.8 ppm, 6 hr ×5×2 | Inhalation | Female and Male | 6–8 | 14/49 | Spleen | lacI | - | [182] |
14/28 | Bone marrow | lacI | + | Ibid | ||||||
Diesel exhaust (DE) | Big Blue rat (F344) | 6Â mg SPM/m3, 12Â hr/day | Inhalation | Male | 6 | 28/31 | Lung | lacI | + | [130] |
1Â mg SPM/m3, 12Â hr/day | Inhalation | Male | 6 | 28/31 | Lung | lacI | - | ibid | ||
80Â mg DEP/kg | Diet | Male | 8 | 21/21 | Lung | cII | - | [131] | ||
20Â mg DEP/kg | Diet | Male | 8 | 21/21 | Lung | cII | - | Ibid | ||
8Â mg DEP/kg | Diet | Male | 8 | 21/21 | Lung | cII | - | Ibid | ||
2Â mg DEP/kg | Diet | Male | 8 | 21/21 | Lung | cII | - | Ibid | ||
0.8Â mg DEP/kg | Diet | Male | 8 | 21/21 | Lung | cII | - | Ibid | ||
0.2Â mg DEP/kg | Diet | Male | 8 | 21/21 | Lung | cII | - | Ibid | ||
Di(2-ethyl-hexyl)phthalate (DEHP) | gpt delta rat (SD) | 12000Â ppm | Diet | Female | 11 | 91/91 | Liver | gpt | - | [167] |
Spi− | - | Ibid | ||||||||
Diethylnitrosamine | gpt delta rat (F344) | 20 mg/kg (once a week) | Intraperitoneal | Male | 7 | 91/91 | Liver | gpt, Spi− | + | [7] |
Male | 7 | 91/91 | kidney | gpt | + | ibid | ||||
5-p-Dimethylaminophenylazobenzthiazole (5BT) | Big Blue rat (F344) | 10 mg/kg ×10 | Gavage | Male | 12 | 10/20 | Liver | lacI | + | [61] |
0.03Â % | Diet | Male | 12 | 10/20 | Liver | lacI | + | ibid | ||
6-p-Dimethylaminophenylazobenzthiazole (6BT) | Big Blue rat (F344) | 10 mg/kg ×10 | Gavage | Male | 12 | 10/20 | Liver | lacI | + | |
0.03Â % | Diet | Male | 12 | 10/20 | Liver | lacI | + | ibid | ||
7,12-Dimethylbenzanthracene (DMBA) | Big Blue rat (F344) | 130Â mg/kg | Gavage | Female | 7 | 1/14 | Splenic lymphocyte | lacI | + | [27] |
1/14 | Mammary gland | lacI | + | [184] | ||||||
1/14 | Bone marrow | lacI | + | [26] | ||||||
1/42 | Splenic lymphocyte | lacI | + | [27] | ||||||
1/42 | Mammary gland | lacI | + | [184] | ||||||
1/42 | Bone marrow | lacI | + | [26] | ||||||
1/70 | Splenic lymphocyte | lacI | + | [27] | ||||||
1/70 | Mammary gland | lacI | + | [18] | ||||||
1/70 | Bone marrow | lacI | + | [26] | ||||||
1/98 | Splenic lymphocyte | lacI | + | [27] | ||||||
1/98 | Mammary gland | lacI | + | [184] | ||||||
1/98 | Bone marrow | lacI | + | [26] | ||||||
80Â mg/kg | Gavage | Female | 7 | 1/112 | Liver | cII | + | [94] | ||
 | Uterus | lacI | + | [96] | ||||||
75Â mg/kg | Gavage | Female | 7 | 1/14 | Splenic lymphocyte | lacI | - | [27] | ||
1/42 | Splenic lymphocyte | lacI | + | Ibid | ||||||
1/70 | Splenic lymphocyte | lacI | + | Ibid | ||||||
1/98 | Splenic lymphocyte | lacI | + | Ibid | ||||||
1/126 | Splenic lymphocyte | lacI | - | Ibid | ||||||
20Â mg/kg | Gavage | Female | 7 | 1/14 | Splenic lymphocyte | lacI | - | [27] | ||
1/14 | Mammary gland | lacI | - | [184] | ||||||
1/14 | Bone marrow | lacI | + | [26] | ||||||
1/42 | Splenic lymphocyte | lacI | + | [27] | ||||||
1/42 | Mammary gland | lacI | - | [184] | ||||||
1/42 | Bone marrow | lacI | + | [26] | ||||||
1/70 | Splenic lymphocyte | lacI | - | [27] | ||||||
1/70 | Mammary gland | lacI | - | [184] | ||||||
1/70 | Bone marrow | lacI | + | [26] | ||||||
1/98 | Splenic lymphocyte | lacI | - | [27] | ||||||
1/98 | Mammary gland | lacI | - | [18]) | ||||||
1/98 | Bone marrow | lacI | + | [26] | ||||||
1/126 | Splenic lymphocyte | lacI | - | [27] | ||||||
1/126 | Mammary gland | lacI | - | [184] | ||||||
Big Blue rat (F344), ovariectomized | 80Â mg/kg | Gavage | Female | 7 | 1/112 | Heart | lacI | + | [185] | |
Liver | cII | + | [94] | |||||||
Uterus | lacI | + | [96] | |||||||
Dimethylnitrosamine (DMN) | Big Blue rat (F344) | 6.0 mg/kg ×9 | Gavage | Male | 12 | 11/12 | Liver | lacI | + | [20] |
cII | + | Ibid | ||||||||
2.0 mg/kg ×9 | Gavage | Male | 12 | 11/12 | Liver | lacI | + | Ibid | ||
cII | + | Ibid | ||||||||
0.6 mg/kg ×9 | Gavage | Male | 12 | 11/12 | Liver | lacI | - | Ibid | ||
cII | - | Ibid | ||||||||
0.2 mg/kg ×9 | Gavage | Male | 12 | 11/12 | Liver | lacI | - | Ibid | ||
cII | - | Ibid | ||||||||
Big Blue rat (F344) | 25Â ppm | Drinking water | Â | Â | 14/14 | Liver | cII | Â | [186] | |
10Â ppm | Drinking water | Â | Â | 14/14 | Liver | cII | Â | Ibid | ||
5Â ppm | Drinking water | Â | Â | 14/14 | Liver | cII | Â | Ibid | ||
1Â ppm | Drinking water | Â | Â | 14/14 | Liver | cII | Â | Ibid | ||
0.1Â ppm | Drinking water | Â | Â | 14/14 | Liver | cII | Â | Ibid | ||
Ellagic acid | Big Blue rat (F344) | 4 g/kg | Diet | Male | 7–10 | 42/42 | Esophagus | lacI | - | [93] |
1,2-Epoxy-3-butene | Big Blue rat (F344) | 29.9 ppm, 6 hr ×5×2 | Inhalation | Female | 6–8 | 14/49 | Spleen | lacI | - | [182] |
14/28 | Bone marrow | lacI | + | Ibid | ||||||
Estragole | gpt delta rat (F344) | 600Â mg/kg | Gavage | Male | 5 | 5Â days per week x 4Â weeks | Liver | gpt | (72) toxic but 2 of 5 survived rats showed positive responses | |
200Â mg/kg | Gavage | Male | 5 | 5Â days per week x 4Â weeks | Liver | gpt | + | ibid | ||
66Â mg/kg | Gavage | Male | 5 | 5Â days per week x 4Â weeks | Liver | gpt | - | Ibid | ||
22Â mg/kg | Gavage | Male | 5 | 5Â days per week x 4Â weeks | Liver | gpt | - | Ibid | ||
N-ethyl-N-nitrosourea (ENU) | Big Blue rat (F344) | 100Â mg/kg | Intraperitoneal | Male | 8+22 | 1/14 | Liver | lacI | + | [102] |
Female | 8+22 | 1/14 | Liver | lacI | + | Ibid | ||||
gpt delta rat (SD) | 100Â mg/kg | Intraperitoneal | Male | 5 | 1/7 | Liver | gpt | + | [17] | |
Spi− | - | Ibid | ||||||||
50 mg/kg ×5 | Intraperitoneal | Male | 10 | 5/7 | Liver | gpt | + | Ibid | ||
5/21 | Liver | gpt | + | Ibid | ||||||
5/35 | Liver | gpt | + | Ibid | ||||||
 |  |  |  | 5/70 | Liver | gpt | + | Ibid | ||
17beta-estradiol | Big Blue rat (F344) | 0.005Â g/kg | Diet | Female | 7 | 112/112 | Mammary gland | lacI | - | [95] |
Uterus | lacI | - | [96] | |||||||
Big Blue rat (F344), ovariectomized | 0.005Â g/kg | Diet | Female | 7 | 112/112 | Heart | lacI | - | [95] | |
Uterus | lacI | - | [96] | |||||||
Ethanol | Big Blue rat (F344) | 5 % | Drinking water | Male | 7–10 | 21/21 | Esophagus | lacI | - | [93] |
Fructose | Big Blue rat (F344) | 30 % | Diet | Male | 9–12 | 35/35 | Liver | cII | - | [101] |
Colon | cII | +− | Ibid | |||||||
Furan | Big Blue rat (F344) | 30Â mg/kg | Gavage | Male | 7 | 56/56 | Liver | cII | - | [187] |
16Â mg/kg | Gavage | Male | 7 | 56/56 | Liver | cII | - | Ibid | ||
8Â mg/kg | Gavage | Male | 7 | 56/56 | Liver | cII | - | Ibid | ||
2Â mg/kg | Gavage | Male | 7 | 56/56 | Liver | cII | - | Ibid | ||
Genistein | Big Blue rat (F344) | 1Â g/kg | Diet | Female | 7 | 112/112 | Mammary gland | lacI | - | [95] |
7 | 112/112 | Liver | cII | - | [94] | |||||
Uterus | lacI | - | [96] | |||||||
0.25Â g/kg | Diet | Female | 7 | 112/112 | Mammary gland | lacI | - | [95] | ||
Uterus | lacI | - | [96] | |||||||
Big Blue rat (F344), ovariectomized | 1Â g/kg | Diet | Female | 7 | 112/112 | Heart | lacI | - | [185] | |
Uterus | lacI | - | [96] | |||||||
Liver | cII | - | [94] | |||||||
0.25Â g/kg | Diet | Female | 7 | 112/112 | Heart | lacI | - | [185] | ||
Uterus | lacI | - | [96] | |||||||
Glass wool fibres | Big Blue rat (F344) | 2Â mg/rat | Intratracheal | Male | 11 | 1/28 | Lung | lacI | - | |
1/112 | Lung | lacI | - | Ibid | ||||||
2Â mg/rat x4 | Intratracheal | Male | 11 | 28/56 | Lung | lacI | - | Ibid | ||
28/133 | Lung | lacI | - | Ibid | ||||||
1Â mg/rat | Intratracheal | Male | 11 | 1/28 | Lung | lacI | - | Ibid | ||
1/112 | Lung | lacI | - | Ibid | ||||||
Glucose | Big Blue rat (F344) | 30 % | Diet | Male | 9–12 | 35/35 | Liver | cII | - | [101] |
Colon | cII | +− | Ibid | |||||||
Glycidamide | Big Blue rat (F344) | 1.4Â mM | Drinking water | Male | 7 | 60/60 | Liver | cII | - | [168] |
Bone marrow | cII | + | Ibid | |||||||
Thyroid | cII | + | Ibid | |||||||
Testis | cII | - | Ibid | |||||||
Female | 7 | 60/60 | Liver | cII | - | Ibid | ||||
Bone marrow | cII | + | Ibid | |||||||
Thyroid | cII | + | Ibid | |||||||
Mammary gland | cII | - | Ibid | |||||||
0.7Â mM | Drinking water | Male | 7 | 60/60 | Liver | cII | - | Ibid | ||
Female | 7 | 60/60 | Liver | cII | - | Ibid | ||||
Hexavalent chromium [Cr(VI)] (as sodium dichromate dihydrate) | Big Blue rat (F344) | 180Â ppm (as Cr(VI)) | Drinking water | Male | 10 | 28/31 | Oral cavity (gingival/bubbal) | cII | - | [189] |
Oral cavity (gingival/palate) | cII | - | Ibid | |||||||
N-hydroxy-2-acetylaminofluorene | Big Blue rat (F344) | 25 mg/kg ×1 | Intraperitoneal | Male | 6 | 1/42 | Liver | lacI | + | |
25 mg/kg ×2 | Intraperitoneal | Male | 6 | 5/42 | Liver | lacI | + | Ibid | ||
25 mg/kg ×4 | Intraperitoneal | Male | 6 | 13/42 | Liver | lacI | + | Ibid | ||
Spleen lymphocytes | lacI | + | Ibid | |||||||
4-Hydroxy-PCB3 (4-OH-PCB3) | Big Blue rat (F344) | 82 mg/kg ×4 | Intraperitoneal | Male | 6 | 22/38 | Liver | lacI | +− | [133] |
Lung | lacI | +− | [135] | |||||||
alpha-Hydroxytamoxifen | Big Blue rat (F344) | 54 μmol/kg ×21 | Intraperitoneal | Female | 8 | 21/51 | Liver | cII | + | [22] |
Liver | lacI | + | [191] | |||||||
Uterus | lacI | - | Ibid | |||||||
0.103 mmol/kg ×10 | Gavage | Female | 6–8 | 10/56 | Liver | lacI | + | [192] | ||
Lard | Big Blue rat (F344) | 30Â % | Diet | Male | 8 | 21/21 | Liver | cII | - | [193] |
Colon | cII | - | Ibid | |||||||
10Â % | Diet | Male | 8 | 21/21 | Liver | cII | - | Ibid | ||
Colon | cII | - | Ibid | |||||||
3Â % | Diet | Male | 8 | 21/21 | Liver | cII | - | Ibid | ||
Colon | cII | - | Ibid | |||||||
Leucomalachite green | Big Blue rat (F344) | 543Â ppm | Diet | Female | 6 | 28/28 | Liver | lacI | - | [79] |
112/112 | Liver | lacI | - | |||||||
 | 224/224 | Liver | lacI | - | [79] | |||||
272Â ppm | Diet | Female | 6 | 28/28 | Liver | lacI | - | Ibid | ||
112/112 | Liver | lacI | - | Ibid | ||||||
224/224 | Liver | lacI | - | Ibid | ||||||
91Â ppm | Diet | Female | 6 | 112/112 | Liver | lacI | - | Ibid | ||
N-Methyl-amyl-nitrosamine | Big Blue rat (Sprague Dawley/Big Blue F1) | 25 mg/kg ×10 | Intraperitoneal |  | 10 | 64/70 | Esophagus | lacI | + | [194] |
3-Methylcholanthrene | Big Blue rat (F344) | 80 mg/kg ×4 | Intraperitoneal | Male | 6 | 22/38 | Liver | lacI | + | [133] |
Lung | lacI | + | [135] | |||||||
4-Monochlorobiphenyl (PCB3) | Big Blue rat (F344) | 113 mg/kg ×4 | Intraperitoneal | Male | 6 | 22/38 | Liver | lacI | + | [133] |
Lung | lacI | + | [135] | |||||||
Madder color and lucidin-3-O-primeveroside (LuP) | gpt delta rat (F344) | Madder color 5.0 % w/w | Diet | Male | 5 | 56/56 | Kidney | gpt, Spi− | + | [73] |
LuP 0.3 % w/w | Diet | Male | 5 | 56/56 | Kidney | gpt, Spi− | + | Ibid | ||
3-MCPD | gpt delta rat (F344) | 40 mg/kg | Gavege | Male | 6 | 5 times per week x 4 weeks/1 | Kidney and testis | gpt, Spi− | - | [66] |
the equimolar esters | Gavege | Male | 6 | Kidney and testis | gpt, Spi− | - | Ibid | |||
Methyleugenol | gpt delta rat (F344) | 100 mg/kg | Gavage | Male and female | 5 | 91/91 | Liver | gpt, Spi− | + | [74] |
30 mg/kg | Gavage | Male and female | 5 | 91/91 | Liver | gpt, Spi− | - | Ibid | ||
10 mg/kg | Gavage | Male and female | 5 | 91/91 | Liver | gpt, Spi− | - | Ibid | ||
Nickel subsulfide (Ni3S2) | Big Blue rat (F344) | 6Â mg/kg (130Â mg/m3), 2Â h | Inhalation | Male | 9 | 1/14 | Lung | lacI | - | [123] |
Nasal mucosa | lacI | - | Ibid | |||||||
gpt delta rat (F344) | 1 mg/animal | Intratracheally instillation | Male | 12 | 28/28 | Lung | gpt, Spi− | - | [124] | |
0.5 mg/animal | Intratracheally instillation | Male | 12 | 28/28 | Lung | gpt, Spi− | - | Ibid | ||
1 mg/animal | Intratracheally instillation | Male | 12 | 90/90 | Lung | gpt, Spi− | - | ibid | ||
0.5 mg/animal | Intratracheally instillation | Male | 12 | 90/90 | Lung | gpt, Spi− | - | Ibid | ||
N-nitrosomethylbenzylamine | Big Blue rat (F344) | 2 mg/kg ×2 | Subcutaneous | Male | 7–10 | 7/21 | Esophagus | lacI | + | [93] |
6-Nitrochrysene | Big Blue rat (F344 × SD)F1 | 100 μmole/rat x 8 | Oral | Female | 5 | 50/274 | Mammary gland | cII | + | [195] |
50 μmole/rat x 8 | Oral | Female | 5 | 50/274 | Mammary gland | cII | + | Ibid | ||
N-nitrosopyrrolidine | gpt delta rat (SD) | 200Â ppm | Drinking water | Female | 11 | 91/91 | Liver | gpt | + | [167] |
4-nitroquinoline-1-oxide | Big Blue rat (F344) | 10 ppm | Drinking water | Male | 10–11 | 28/31 | Oral cavity (gingival/bubbal) | cII | + | [196] |
Oral cavity (gingival/palate) | cII | + | Ibid | |||||||
Liver | cII | - | Ibid | |||||||
Bone marrow | cII | - | Ibid | |||||||
Big Blue rat (F344) | 10Â ppm | Drinking water | Male | 10 | 28/31 | Oral cavity (gingival/bubbal) | cII | + | [189] | |
Oral cavity (gingival/palate) | cII | + | Ibid | |||||||
Ochratoxin A | gpt delta rat (F344) | 5Â ppm | Diet | Male and female | 5 | 28/28 | outer medulla of kidney | gpt | - | [50] |
Male and female | 5 | 28/28 | outer medulla of kidney | Spi− | + | Ibid | ||||
Male and female | 5 | 91/91 | whole kidney | gpt, Spi− | - | ibid | ||||
5 ppm | Diet | Male | 5 | 28/28 | outer medulla of kidney | Spi− | + | [65] | ||
Phenacetin | gpt delta rat (SD) | 0.50 % | Diet | Male and female | 7 | 182/182 | Kidney | gpt, Spi− | - | [52] |
Male and female | 7 | 182/182 | Liver | gpt | + | Ibid | ||||
Male and female | 7 | 182/182 | Liver | Spi− | - | ibid | ||||
Male | 7 | 364/364 | Kidney | gpt | + | Ibid | ||||
Male | 7 | 364/364 | Kideney | Spi− | - | Ibid | ||||
Female | 7 | 364/364 | Kideney | gpt, Spi− | - | Ibid | ||||
Male | 7 | 364/364 | Liver | gpt, Spi− | + | Ibid | ||||
Female | 7 | 364/364 | Liver | gpt, Spi− | + | Ibid | ||||
Potassium Bromate (KBrO3) | Big Blue rat (F344) | 500Â ppm | Drinking water | Male | 6 | 112/112 | Kidney | lacI | + | [87] |
125Â ppm | Drinking water | Male | 6 | 112/112 | Kidney | lacI | - | Ibid | ||
30Â ppm | Drinking water | Male | 6 | 112/112 | Kidney | lacI | - | Ibid | ||
8Â ppm | Drinking water | Male | 6 | 112/112 | Kidney | lacI | - | Ibid | ||
2Â ppm | Drinking water | Male | 6 | 112/112 | Kidney | lacI | - | Ibid | ||
0.2Â ppm | Drinking water | Male | 6 | 112/112 | Kidney | lacI | - | Ibid | ||
0.02Â ppm | Drinking water | Male | 6 | 112/112 | Kidney | lacI | - | Ibid | ||
0.002Â ppm | Drinking water | Male | 6 | 112/112 | Kidney | lacI | - | Ibid | ||
gpt delta rat (SD) | 500Â ppm | Drinking water | Male | 5 | 7/7 | Kidney | gpt | - | [119] | |
Spi− | - | Ibid | ||||||||
35/35 | Kidney | gpt | - | Ibid | ||||||
Spi− | - | Ibid | ||||||||
63/63 | Kidney | gpt | - | Ibid | ||||||
Spi− | + | Ibid | ||||||||
91/91 | Kidney | gpt | - | Ibid | ||||||
Spi− | + | Ibid | ||||||||
250Â ppm | Drinking water | Male | 5 | 91/91 | Kidney | gpt | - | Ibid | ||
Spi− | - | Ibid | ||||||||
125Â ppm | Drinking water | Male | 5 | 91/91 | Kidney | gpt | - | Ibid | ||
Spi− | - | Ibid | ||||||||
60Â ppm | Drinking water | Male | 5 | 91/91 | Kidney | gpt | - | Ibid | ||
Spi− | - | Ibid | ||||||||
gpt delta rat (F344) | 500Â ppm | Drinking water | Male | 5 | 63/63 | Kidney | gpt | - | [120] | |
Spi− | - | Ibid | ||||||||
Female | 5 | 63/63 | Kidney | gpt | + | Ibid | ||||
Spi− | - | Ibid | ||||||||
Riddelliine | Big Blue rat (F344) | 1.0 mg/kg ×5 ×12 | Gavage | Female | 6 | 82/83 | Liver | cII | + | [115] |
0.3 mg/kg ×5 ×12 | Gavage | Female | 6 | 82/83 | Liver | cII | + | ibid | ||
6 | 82/83 | Liver parenchymal cells | cII | - | [116] | |||||
6 | 82/83 | Liver endothelial cells | cII | + | Ibid | |||||
0.1 mg/kg ×5 ×12 | Gavage | Female | 6 | 82/83 | Liver | cII | + | [115] | ||
Rock wool fibers | Big Blue rat (F344) | 2Â mg/rat | Intratracheal | Male | 11 | 1/28 | Lung | lacI | - | |
1/112 | Lung | lacI | + | Ibid | ||||||
2 mg/rat ×4 | Intratracheal | Male | 11 | 28/56 | Lung | lacI | - | Ibid | ||
28/133 | Lung | lacI | + | ibid | ||||||
1Â mg/rat | Intratracheal | Male | 11 | 1/28 | Lung | lacI | - | Ibid | ||
1/112 | Lung | lacI | + | Ibid | ||||||
Selenium (as sodium selenite) with dimethylhydrazine (DMH) injection | Big Blue rat (F344) | 2 μg Se/g diet with DMH injection | Diet |  |  | 63–84/63–84 (DMH (25 mg/kg body weight, i.p., weekly, twice) was injected after 3 weeks of the diet. | Liver | cII | + | [197] |
Colon | cII | + | Ibid | |||||||
0.2 μg Se/g diet with DMH injection | Diet |  |  | 63–84/63–84 (DMH (25 mg/kg body weight, i.p., weekly, twice) was injected after 3 weeks of the diet. | Liver | cII | + | Ibid | ||
Colon | cII | + | Ibid | |||||||
*No effect of Se. | ||||||||||
Sucrose | Big Blue rat (F344) | 30 % | Diet | Male | 9–12 | 35/35 | Liver | cII | - | [101] |
Colon | cII | +− | Ibid | |||||||
34.50 % | Diet | Male | 8–12 | 21/21 | Liver | cII | - | [136] | ||
Colon | cII | + | ibid | |||||||
13.80 % | Diet | Male | 8–12 | 21/21 | Liver | cII | - | Ibid | ||
Colon | cII | + | Ibid | |||||||
6.90 % | Diet | Male | 8–12 | 21/21 | Liver | cII | - | Ibid | ||
Colon | cII | - | Ibid | |||||||
13.40 % | Diet | Male | 9–12 | 21/21 | Liver | cII | - | [100] | ||
Colon | cII | + | Ibid | |||||||
3.45 % | Diet | Male | 9–12 | 21/21 | Liver | cII | - | Ibid | ||
Colon | cII | + | Ibid | |||||||
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) | Big Blue rat (F344) | 2 μig/kg ×12 | Gavage | Male | 8 | 42/56 | Liver | lacI | - | [128] |
Female | 8 | 42/56 | Liver | lacI | - | Ibid | ||||
Tamoxifen | Big Blue rat (F344) | 54 μmol/kg ×21 | Intraperitoneal | Female | 8 | 21/51 | Liver | cII | + | [22] |
Liver | lacI | + | [191] | |||||||
Uterus | lacI | - | Ibid | |||||||
20 mg/kg ×42 | Gavage | Female | 6–8, 16–18 | 42/56 | Liver | lacI | + | [170] | ||
 | cII | + | [109] | |||||||
6–8 | 42/42 | Liver | lacI | + | [110] | |||||
42/56 | Liver | lacI | + | Ibid | ||||||
42/126 | Liver | lacI | + | Ibid | ||||||
42/210 | Liver | lacI | + | Ibid | ||||||
10 mg/kg ×42 | Gavage | Female | 6–8 | 42/56 | Liver | lacI | + | [170] | ||
 |  | cII | +− | [109] | ||||||
gpt delta rat (F344) | 40 mg/kg | Gavege | Female | 21/21 | Liver | gpt, Spi− | + | [58] | ||
Gavege | Female | 21/21 | Kidney | gpt, Spi− | - | Ibid | ||||
20 mg/kg | Gavege | Female | 21/21 | Liver | gpt, Spi− | + | Ibid | |||
Gavege | Female | 21/21 | Kidney | gpt, Spi− | - | Ibid | ||||
500 ppm | Diet | Female | 91/91 | Liver | gpt, Spi− | + | Ibid | |||
Diet | Female | 91/91 | Kidney | gpt, Spi− | - | Ibid | ||||
250 ppm | Diet | Female | 91/91 | Liver | gpt, Spi− | + | Ibid | |||
Diet | Female | 91/91 | Kidney | gpt, Spi− | - | Ibid | ||||
Thiotepa Toremifene | Big Blue rat (F344) | 1.4 mg/kg ×12 | Intraperitoneal | Male | 7 | 28/35 | Spleen lymphocytes | lacI | + | [29] |
Big Blue rat (F344) | 20 mg/kg ×42 | Gavage | Female | 6–8 | 42/56 | Liver | lacI | - | [170] | |
gpt delta rat (F344) | 40 mg/kg | Gavege | Female | 21/21 | Liver | gpt, Spi− | - | [58] | ||
Gavege | Female | 21/21 | Kidney | gpt, Spi− | - | Ibid | ||||
Tris(2,3-dibromopropyl)phosphate (TDBP) | Big Blue rat (F344) | 2000 ppm | Diet | Male | 6–8 | 45/45 | Kidney (outer medulla) | lacI | + | [47] |
Kidney (inner medulla) | lacI | + | Ibid | |||||||
Kidney (cortex) | lacI | + | Ibid | |||||||
100 ppm | Diet | Male | 6–8 | 45/45 | Kidney (outer medulla) | lacI | + | Ibid | ||
Kidney (inner medulla) | lacI | + | Ibid | |||||||
Kidney (cortex) | lacI | + | Ibid | |||||||
Uracil | Big Blue rat (F344) | 3Â % | Diet | Male | 6 | 14/14 | Bladder | lacI | - | [25] |
70/70 | Bladder | lacI | + | Ibid | ||||||
140/140 | Bladder | lacI | + | Ibid | ||||||
357/357 | Bladder | lacI | + | Ibid |