Assays of three carcinogen/non-carcinogen chemical pairs for in vivo induction of chromosome aberrations, sister chromatid exchanges and micronuclei.
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.
McFee
A F
AF
Medical Sciences Division, Oak Ridge Associated Universities, Tennessee 37831-0117.
Jauhar
P P
PP
Lowe
K W
KW
MacGregor
J T
JT
Wehr
C M
CM
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000648:ultrastructure; D002273:Carcinogens / Q000032:analysis / Q000633:toxicity*; D002869:Chromosome Aberrations; D004912:Erythrocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests; D010655:Phenylenediamines / Q000633:toxicity; D011725:Pyridines / Q000633:toxicity; D012854:Sister Chromatid Exchange; D013329:Structure-Activity Relationship; D014052:Toluidines / Q000633:toxicity; D062367:ortho-Aminobenzoates / Q000633:toxicity
D002273:Carcinogens; D010655:Phenylenediamines; D011725:Pyridines; D014052:Toluidines; D062367:ortho-Aminobenzoates; C012277:1,2-diamino-4-nitrobenzene; C015060:4-chloro-1,2-diaminobenzene; C051822:3-(chloromethyl)pyridine; C023622:2-toluidine