Assays of three carcinogen/non-carcinogen chemical pairs for in vivo induction of chromosome aberrations, sister chromatid exchanges and micronuclei.

A F McFee, P P Jauhar, K W Lowe, J T MacGregor, C M Wehr

Index: Environ. Mol. Mutagen. 14(4) , 207-20, (1989)

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Abstract

Three pairs of structurally similar carcinogenic/non-carcinogenic chemicals were tested for in vivo genotoxic activity in B6C3F1 mice. The carcinogenic/non-carcinogenic pairs, respectively, were o-toluidine hydrochloride/o-anthranilic acid, 4-chloro-o-phenylenediamine/4-nitro-o-phenylenediamine, and 3-(chloromethyl)pyridine hydrochloride/2-(chloromethyl)pyridine hydrochloride. Bone marrow cells from mice given intraperitoneal injections of up to the maximum tolerated dose were evaluated for chromosomal aberration, sister chromatid exchange, and micronucleus induction, o-anthranilic acid and o-toluidine hydrochloride did not increase the frequency of chromosomal aberrations or micronuclei. o-Toluidine hydrochloride increased the frequency of sister chromatid exchanges in two successive trials, while o-anthranilic acid had a positive effect on sister chromatid exchanges in two of three trials. Both 2-(chloromethyl) and 3-(chloromethyl)pyridine hydrochloride were negative for all three endpoints. Assays for chromosomal aberrations and micronuclei each distinguished between 4-chloro-o-phenylenediamine and its non-carcinogenic companion, 4-nitro-o-phenylenediamine. In the aberration test, 4-chloro-o-phenylenediamine produced a few cells with very large numbers of aberrations rather than an even distribution of damage among cells.