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The induction of bacterial mutation and hepatocyte unscheduled DNA synthesis by monosubstituted anilines
Abstract:
A group of 45 monosubstituted aniline compounds was tested for the induction of point mutations in Salmonella typhimurium and Escherichia coli as well as for unscheduled DNA synthesis (UDS) in rat hepatocyte culture. Eleven compounds were bacterial mutagens, and five compounds induced UDS. Among these a correspondence between mutagenicity and UDS occurred for only two compounds (o-phenylenediamine and 4-aminobiphenyl), and these were also reported to be carcinogenic in rodents. Bacterial mutation was observed for one compound (p-phenylenediamine) not carcinogenic in rodents, and six suspect carcinogens were not detected in either test. In addition, eight compounds of unknown carcinogenic potential induced either bacterial mutation or UDS.
Insights
This study evaluated 45 aniline compounds for mutagenicity and DNA synthesis induction. Some compounds showed mutagenic or DNA-damaging potential, with limited correlation to rodent carcinogenicity, highlighting complex toxicological profiles.
Area of Science:
- Toxicology
- Genotoxicity
- Chemical Carcinogenesis
Background:
- Monosubstituted anilines are widely used industrial chemicals.
- Assessing their genotoxic and carcinogenic potential is crucial for risk assessment.
Purpose of the Study:
- To evaluate the mutagenic activity of 45 monosubstituted anilines in bacterial assays.
- To assess the potential of these compounds to induce unscheduled DNA synthesis (UDS) in rat hepatocytes.
- To investigate the correlation between bacterial mutagenicity, UDS induction, and rodent carcinogenicity data.
Main Methods:
- Bacterial reverse mutation assay using Salmonella typhimurium and Escherichia coli.
- Unscheduled DNA synthesis (UDS) assay in primary rat hepatocyte cultures.
- Comparison of in vitro genotoxicity data with existing rodent carcinogenicity classifications.
Main Results:
- Eleven compounds induced bacterial mutations; five induced UDS.
- A strong correlation between mutagenicity and UDS was observed for only two compounds (o-phenylenediamine and 4-aminobiphenyl), both known rodent carcinogens.
- One compound (p-phenylenediamine), not carcinogenic in rodents, was mutagenic. Six suspect carcinogens were negative in both assays.
- Eight compounds of unknown carcinogenic potential showed positive results in either the bacterial mutation or UDS assay.
Conclusions:
- In vitro genotoxicity assays identified several monosubstituted anilines with mutagenic or DNA-damaging potential.
- The correlation between mutagenicity, UDS, and rodent carcinogenicity is compound-specific and not universally predictive.
- Further investigation is warranted for compounds showing genotoxicity but lacking carcinogenicity data.