Flow cytometric micronucleus assay and TGx-DDI transcriptomic biomarker analysis of ten genotoxic and non-genotoxic chemicals in human HepaRG™ cells

Table 2 MN frequency and TGx-DDI classification for test chemicals using NSC probability analysis, principal component analysis, and 2-dimensional clustering

Test Chemical	MN Induction			Overall TGx-DDI Classification			PA Classification			PCA Classification			2 DC Classification
Test Chemical	Low	Mid	High	Low	Mid	High	Low	Mid	High	Low	Mid	High	Low	Mid	High
DDI Chemicals
Aflatoxin B1	+	+	+	Non-DDI	DDI	DDI	Non-DDI	DDI	DDI	Non-DDI	DDI	DDI	Non-DDI	Non-DDI	DDI
Cisplatin	–	+	+	Non-DDI	Non-DDI	DDI	Non-DDI	Non-DDI	DDI	Non-DDI	Non-DDI	DDI	Non-DDI	Non-DDI	Non-DDI
Etoposide	+	+	+	DDI	DDI	DDI	DDI	DDI	DDI	Non-DDI	DDI	DDI	Non-DDI	Non-DDI	Non-DDI
Methyl methanesulfonate	–	+	+	Non-DDI	DDI	DDI	Non-DDI	DDI	DDI	Non-DDI	DDI	DDI	Non-DDI	DDI	DDI
2-Nitrofluorene	–	+	+	Non-DDI	DDI	DDI	Non-DDI	DDI	DDI	Non-DDI	DDI	DDI	Non-DDI	DDI	DDI
Non-DDI Chemicals
Ampicillin Trihydrate	–	–	–	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI
Colchicine	–	+	+	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI
2-Deoxy-D-Glucose	–	–	–	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI
Sodium Ascorbate	–	–	–	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI
Sodium Chloride	–	–	–	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI	Non-DDI

For MN Induction, a ‘+’ sign indicates a statistically significant induction of MN and at least a two-fold change over vehicle controls and a ‘-‘sign indicates that there was no statistically significant induction of MN. For the TGx-DDI classification results, DDI represents a DNA damage-inducing classification; whereas, non-DDI represents a non-DNA damage-inducing classification. The ‘overall’ DDI call requires a DDI call in at least one of the three analyses (PA, 2 DC, PCA), whereas a non-DDI is non-DDI in all of these analyses

ISSN: 1880-7062