Selective induction of micronuclei in the rat/mouse colon and liver by 1,2-dimethylhydrazine: a seven-tissue comparative study.

1,2-Dimethylhydrazine (DMH) was administered to both genders of mice and rats by oral gavage for 3 days. Twenty-four hours later, an assessment of the incidence of micronucleated cells was made in the bone marrow and sections of the gastrointestinal tract. An increase in micronucleated cells was observed in the colon of both genders of both species of rodent. Negative responses were observed in the forestomach, stomach, duodenum, intestine of both species. The bone marrow micronucleus assays were essentially negative, but the absence of a precise definition of the MTD precludes a definitive conclusion from being drawn. These results are consistent with the selective carcinogenicity of DMH to the colon of the rodent GI-tract. DMH is also known to be carcinogenic to rat and mouse liver and, although it is known to induce micronuclei in the hepatocytes of rats, no such data exist for the mouse. Consequently, mice were administered DMH on 13 successive days, followed by 2/3 partial hepatectomy and assessment of micronucleated hepatocytes. A strong positive liver micronucleus assay response was observed. Thus, DMH selectively induces micronuclei in the colon and liver of rats and mice, consistent with its carcinogenicity to these two tissues. No qualitative differences between the genders was observed in any of the assays. These results indicate that the assessment of genetic toxicity in rodents should not rely solely on assays made in bone marrow.

Genotoxicity and carcinogenicity testing of 1,2-dibromopropane and 1,1,3-tribromopropane in comparison to 1,2-dibromo-3-chloropropane.

The activities of 1,2-dibromopropane (DBP) and 1,1,3-tribromopropane (TBP) were studied in seven genotoxicity assays, (i) SOS-induction in E. coli, (ii) DNA repair in primary rat hepatocyte culture, (iii) the Salmonella/microsome assay, (iv) a host-mediated assay using Salmonella, (v) the somatic mutation and recombination assay in Drosophila melanogaster, (vi) HGPRT-mutagenesis assay in ARL 18 cells, and (vii) micronucleus formation assay in mouse polychromatophylic erythrocytes (PCE), forestomach (FS), glandular stomach (GS), duodenum (D), jejunum (J), cecum (C) and liver (L). The halopropanes were also tested for tumor formation in the fish Danio rerio. DBP was active in assays (ii), (v), (vii FS) and (vii L). TBP was positive in assays (ii) and (iii), strongly positive in (vii L) and borderline positive in (iv). However, neither DBP nor TBP induced tumors in fish, in contrast to the carcinogenic 1,2-dibromo-3-chloropropane. The genotoxicity and potential carcinogenicity of DBP and TBP in mammals is discussed.

[Mutagenic activity of the fungicide captan]. / K voporsu o mutagennoi aktivnosti fungitsida kaptana.

A complex study of mutagenic activity of captan (a fungicide) in a series of standard test-systems has shown that the preparation induces gene mutations in certain Salmonella indicator strains (without metabolic activation), increases the frequency of mitotic crossing-over and gene conversion in yeasts (Saccharomyces), possesses a weak cytogenetic action on bone marrow cells in experimental animals, manifests no cytogenetic effect in the lymphocyte culture of human peripheral blood (including a system of microsomal activation). Genetic activity of captan cannot be a limiting criterion of its harmfulness.

[Effect of phenobarbital on the cytogenetic activity of cyclophosphamide]. / Vliianie fenobarbitala na tsitogeneticheskuiu aktivnost' tsiklofosfamida.

The effect of phenobarbital (PB, 2 and 80 mg/kg, 3 intraperitoneal injections) on the rate of chromosomal aberrations in the bone marrow cells of rats induced by a single intraperitoneal injection of cyclophosphamide (CP) in a dose of 25 mg/kg was studied. Activity of mixed function oxygenase (MFO) was evaluated from the content of cytochrome P450, b5 and activity of aniline hydroxylase. The rate of the cells with chromosomal aberrations in the bone marrow after combined action of PB and CP did not depend on the PB dose and was significantly higher as compared with CP action alone. After injection of 2 mg/kg, PB activity of MFO did not differ from that in control and increased 2 times after 80 mg/kg. Combined action of PB and CP did not induce any significant changes in activity of MFO compared with PB alone.