Induction of chromosomal aberrations and sister-chromatid exchanges in Chinese hamster cells in vitro by some proximate and ultimate carcinogenic arylamide derivatives.

The carcinogenic compounds N-hydroxy-N-acetyl-2-aminofluorene, N-acetoxy-N-acetyl-2-aminofluorene, N-hydroxy-N-acetyl-4-aminobiphenyl and N-acetoxy-N-acetyl-4-aminobiphenyl were studied for their ability to induce chromosomal aberrations and sister-chromatic exchanges in Chinese hamster ovary cells in the presence and absence of a rat-liver microsomal system. The O-acetates of N-hydroxy-N-acetyl-2-aminofluorene and N-hydroxy-N-acetyl-4-aminobiphenyl induced chromosomal aberrations in a population of cells samples at 22--25 h after treatment. The N-hydroxy arylacetamides did not produce detectable increases in chromosomal aberrations when tested at 22--25 h after treatment, but micronuclei that had arisen from acentric fragments at the first mitosis were demonstrable in second-division cells fixed between 30 and 33 h after treatment. N-Acetoxy-N-acetyl-2-aminofluorene appeared to be a more effective inducer of chromosomal damage than the corresponding biphenyl derivative. All O-acetates and N-hydroxy derivatives induced sister-chromatid exchanges. N-Acetoxy-N-acetyl-4-aminobiphenyl and N-hydroxy-N-acetyl-4-aminobiphenyl were equally effective, whereas N-acetoxy-N-acetyl-2-aminofluorene was a better inducer of sister-chromatid exchanges than N-hydroxy-N-acetyl-2-aminofluorene. Simultaneous treatment of cells with O-acetates and S9 mix decreased the effectivity to induce chromosomal damage as compared to treatment with O-acetates alone. In one experiment where the organic solvent DMSO was used at the concentration of 10% in combination with S9 mix, substantial amounts of chromosomal aberrations were induced.

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