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The genotoxicity of a variety of hydrazine derivatives was examined in the DNA-repair test on rat or mouse hepatocytes. Out of 32 hydrazine derivatives, 6 chemicals, i.e., N-acetyl-4-(hydroxymethyl)phenylhydrazine, 1,2-dimethylhydrazine - 2HCl, 1-hydrazinophthalazine - HCl, methylhydrazine-sulfate, p, p′-oxybisbenzene disulfonylhydrazide and phenylhydrazine-HCl, elicited positive DNA repair responses in the test on rat hepatocytes. In the test on mouse hepatocytes, 4 more hydrazine derivatives, i.e., 1,1-dimethylhydrazine, hydrazine hydrate, hydrazine sulfate and 2-methyl-4-chlorophenoxyacetic acid hydrazide-HCl also generated positive responses, in addition to the 6 positive compounds in the rat assay. These results suggest that mouse hepatocytes are more susceptible to the genotoxicity of hydrazine derivatives, and that the species differences in genotoxicity appear to he in agreement with the in vivo carcinogenicity of these agents.

The micronucleus test is used widely as an in vivo short-term assay for potential carcinogens. In the present study, results of the micronucleus test were affected by the rate of erythropoiesis in the bone marrow erythropoietin, a growth factor for the erythroblast, which was used to induce erythropoiesis. The highest frequency of micronucleated polychromatic erythrocytes (MPCE) and a dose-response relationship between erythropoietin doses and MPCE frequency were seen 30 hr after injection of 1,1-dimethylhydrazine (DMH) to mice administered 24 hr previously with erythropoietin. The effect of erythropoietin was maximal when erythropoietin was given 24 hr before DMH, indicating that accelerating the multiplication of erythroblasts will increase the frequency of micronuclei induced by mutagens. Induction of MPCE in the bone marrow by four other compounds—benzo(a)pyrene,2-naph-thylamine, mitomycin C, and vincristine—was also increased by pretreatment with erythropoietin.

Mutagenicity of seven aromatic amines, two heterocyclic amines, two azo compounds and one polycyclic aromatic hydrocarbon was examined with the fluctuation test modified by Gatehouse. The test was performed by using Salmonella typhimurium TA98 and TA100 in the presence of bladder S9 from PCB-pretreated rats.Seven out of 12 compounds were found to be mutagenic to TA98 or TA100, but three were negative for both bacterial strains. 3-Amino-1, 4-dimethyl-5H-pyrido [4, 3-b] indole and 3-amino-1-methyl-5H-pyrido [4, 3-b] indole (Trp-P-2) showed mutagenicity at the lowest concentration, when compared with other compounds. 2-Aminofluorene (2-AF) tested with TA98 revealed an increment of positive wells compared with other compounds at the same dosage. A dose-related increment of mutagenic activity was observed with 3-methylcholanthrene by TA100 and Trp-P-2 and 2-AF by TA98.Based on this experiment, we suggest that aromatic amines, heterocyclic amines and polycyclic aromatic hydrocarbons can be metabolized to mutagenic compounds by rat bladder S9 pretreated with PCB. The fluctuation test using bladder S9 is useful for investigating the mutagenic activity of chemicals which are capable of inducing bladder tumors.