The genotoxicity of various chemicals and complex mixtures was evaluated through a study of micronuclei induction using mouse- BALB/c-3T3 cells. The chemicals tested were benzo(a)pyrene (50328) (BAP), cyclophosphamide (50180) (CPA), 2-aminoanthracene (613138) (2AA), 2-nitrofluorene (607578) (2NF). The complex mixtures tested were cigarette smoke condensate (CSC) and nitrosated coal dust extracts (CDE). BALB/c-3T3 subclone A31-1-13 cells were seeded at a density of about 10(6) cells/dish and exposed to the chemicals for various lengths of time. Cytogenetic preparations were scored for micronuclei using 2000 interphase cells. Results showed that all tested chemicals and mixtures induced micronuclei. With BAP, CPA, 2AA and 2NF, increased frequencies of micronuclei were observed at concentrations that did not induce cytotoxicity. Except for CSC and CDE, differences between treated groups and solvent controls were significant. Both CSC and CDE were toxic at high concentrations. Dose response relationships showed correlation coefficients higher than 0.80, except for BAP which was 0.46. BAP and CPA tested for exposure times of 8 hour (hr) and 24hr, and 4hr and 8hr, respectively, showed that the longer exposure did not result in a consistent increase in induced micronuclear frequencies. The authors conclude that BALB/c-3T3 cells are capable of activating all the tested chemicals to act as procarcinogens and promutagens, and that this system may prove to be useful for screening genotoxic chemicals since the frequencies of micronuclei produced are higher than those in Chinese-hamster-V79 cells.
NIOSH-Author; Carcinogens; In-vitro-studies; Metabolism; Mutagens; Pollutants; Screening-methods; Genotoxic-effects; Mammalian-cells; Tobacco-smoke;
Author Keywords: Micronucleus assay; Metabolic activation; BALB/c-3T3 cell; Benzo[a]pyrene; Cyclophosphamide; 2-Aminoanthracene; 2-Nitrofluorene; Complex mixtures