ABSTRACT
CAP and ZOIN were tested in vivo for their ability to induce sister-chromatid exchanges (SCE) and chromosome aberrations in mouse bone marrow cells. Single intraperitoneal injections of ZOIN to a maximum of 3000 mg/kg body weight failed to increase the number of SCEs in metaphases recovered 24 h post-treatment, and doses of 1500 mg/kg did not induce measurable increases in chromosome-aberration levels among first-division metaphases at 18 h. Similarly, neither endpoint showed a significant increase following near-lethal doses of 700 mg/kg of CAP. Two lower doses of each chemical were also ineffective. Under the in vivo conditions of our test system, both chemicals were cytogenetically inactive.
Subject(s)
Azepines/toxicity , Benzoin/toxicity , Bone Marrow/drug effects , Caprolactam/toxicity , Chromosome Aberrations , Mutagens , Sister Chromatid Exchange/drug effects , Animals , Male , MiceABSTRACT
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.
Subject(s)
Bone Marrow/drug effects , Carcinogens/toxicity , Chromosome Aberrations , Micronuclei, Chromosome-Defective , Sister Chromatid Exchange , Animals , Bone Marrow/ultrastructure , Carcinogens/analysis , Erythrocytes/drug effects , Male , Mice , Micronucleus Tests , Phenylenediamines/toxicity , Pyridines/toxicity , Structure-Activity Relationship , Toluidines/toxicity , ortho-Aminobenzoates/toxicityABSTRACT
Sister-chromatid exchange (SCE) frequencies were determined for mouse and rabbit bone-marrow cells following incorporation of 3 different halogenated analogues of thymidine. For both species the SCE frequency was highest for chlorodeoxyuridine, lowest for iododeoxyuridine and intermediate for bromodeoxyuridine. The study demonstrates that halogenated pyrimidine analogues other than brominated compounds can be used for in vivo SCE analysis and that their effects on baseline SCE frequencies are qualitatively similar to results of previous in vitro studies.
