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. Author manuscript; available in PMC: 2023 Oct 17.
Published in final edited form as: Chem Res Toxicol. 2022 Aug 31;35(10):1747–1765. doi: 10.1021/acs.chemrestox.2c00175

Table 3.

Mutagenicity of Nitro-Containing Compounds at the HPRT Locus in V79 Chinese Hamster Lung Cells

Nitro-Containing Compounda V79 Cell Derivative Used Mutant Frequency/106 Cells Conclusion Ref IARC Classification
1-Nitropyrene (1-NP) (3 μM) V79-NH1A2
(V79 cells expressing NAT and CYP1A2)
83 ± 34 (SD) 1-NP treated cells
7 ± 11 (SD) untreated cells
1-NP was mutagenic in V79-NH1A2 cells containing NAT and CYP1A2 activity but not in V79-NH cells containing only NAT 154 2A (probable human carcinogen)
1-Nitropyrene (1-NP) (50 μM) V79 cells in the presence or absence of rat S9 or rat S100 18.3 1-NP treated cells
72.8 1-NP treated cells + S9
15.3 1-NP treated cells + S100
10.4 untreated cells
1-NP was only mutagenic in V79 cells in the presence of S9 but not S100 128 2A (probable human carcinogen)
1,8-Dinitropyrene (1,8-DNP) (17.1 μm) V79 (no additional enzymes expressed) 14.2—20.2 1,8-DNP treated cells
1.4—27.6 in untreated cells
1,8-DNP was not mutagenic in V79 cells at the conditions tested 130 2B (possible human carcinogen)
2-Nitrofluorene (2-NF) (10 μM, 30 μM) V79-NH1A2, V79-NH2C9 (V79 cells expressing NAT activity and CYP1A2, or V79 cells expressing NAT activity and CYP2C9, respectively) No statistically significant difference in V79-NH1A2 cells and V79-NH2C9 cells exposed to 2-NF when compared to untreated cells. The same was shown for V79-NH cells that contain NAT but do not express CYP1A2 or CYP2C9 2-NF was not mutagenic in V79-NH1A2, V79-NH2C9 or V79-NH cells at the conditions tested 154 2B (possible human carcinogen)
2-Nitrobenzanthrone (2-NBA) (1 μM) V79-hSULT1A1 (V79 cells that express human SULT1A1) 150 2-NBA treated cells
0 in V79 hSULT1A1 in untreated cells
0 in V79 cells lacking hSULT1A1 or hNAT2
SULT1A1 contributed to mutagenicity at the HPRT locus in cells exposed to 2-NBA. 129 N/A
2-Nitrobenzanthrone (2-NBA) (1 μM) V79-hNAT2 (V79 cells that express human NAT2) 110 in 2-NBA treated cells
0 in V79-hNAT2 in untreated cells
0 in V79 cells lacking hSULT1A1 or hNAT2
NAT2 contributed to mutagenicity at the HPRT locus in cells exposed to 2-NBA. 129 N/A
3-Nitrofluoranthene (3-NFA) (100 μM) V79 cells in the presence or absence of rat S9 or rat S100 14.9 Cells treated with 3-NFA
25.0 Cells treated with 3-NFA + S9
175.7 Cells treated with 3-NFA + S100
10.4 Untreated cells
3-NFA was mutagenic in V79 cells in the presence of S100 more so than in the presence of S9 128 3 (human carcinogenicity not classifiable)
8-Nitrofluoranthene (8-NFA) (25 μM) V79 cells in the presence or absence of rat S9 or rat S100 12.8 Cells treated with 8-NFA
21.5 Cells treated with 8-NFA + S9
1378 Cells treated with 8-NFA + S100
10.4 Untreated cells
8-NFA was mutagenic in V79 cells in the presence of S100 more so than in the presence of S9 128 N/A
Aristolochic acids (38% aristolochic acid I, 58% aristolochic acid II) (40 μM) V79-hSULT1A1 (V79 cells that express human SULT1A1) 250 in treated cells.
80 in V79 cells lacking hSULT1A1
0 in V79-hSULT1A1 in untreated cells
SULT1A1 contributed to mutagenicity at the HPRT locus in cells exposed to a mixture of aristolochic acids 155 1 (carcinogenic to humans)
Aristolochic acids (38% aristolochic acid I, 58% aristolochic acid II) (40 μM) V79-hCYP2E1-hSULT1A1 (V79 cells that coexpress human CYP2E1 and SULT1A1) 1300 in treated cells
350 in V79-hCYP2E1-hSULT1A1 cells treated additionally with 10 μM pentachlorophenol, a SULT1A1 inhibitor, 0 in V79-hCYP2E1-hSULT1A1 untreated cells
Coexpression of SULT1A1 and CYP2E1 increased mutagenicity at the HPRT locus in cells exposed to a mixture of aristolochic 155 1 (carcinogenic to humans)
Metronidazole, nimorazole, tinidazole, niridazole (each from 0 to 1 mM) V79 cells and V79 cells cultured with freshly isolated and uninduced Sprague–Dawley male rat hepatocytes No statistically significant difference for any of the compounds in V79 cells or V79 cells cultured with rat hepatocytes Metronidazole, nimorazole, tinidazole, and niridazole were not mutagenic at the conditions tested. 156 Metronidazole (2B); nimorazole (N/A); tinidazole (N/A); niridazole (2B)
a

The concentrations reported correspond to the highest concentrations used in the studies or the concentrations giving maximum or near maximum response observed. N/A in the IARC classification column indicates that the compound has not been classified by IARC for human carcinogenicity.