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.

No abstract

Establishment of an animal model of stomach carcinogenesis in mice was attempted using N‐methyl‐N‐nitrosourea (MNU) in the drinking water. One hundred and forty‐eight male 6‐week‐old C3H mice were given MNU in their drinking water at a concentration of 120 ppm (group 1), 60 ppm (group 2), 30 ppm (group 3) or 0 ppm (group 4) for 30 weeks. At the end of this time, dose‐related induction of adenomatous hyperplasias was found. From weeks 31 to 54 adenocarcinomas developed in a dose‐dependent manner in groups 1, 2 and 3. In total, 6 well differentiated and 5 poorly differentiated adenocarcinomas as well as 6 signet ring cell carcinomas arose in 15 stomach cancer‐bearing animals in group 1, 4 well differentiated and 2 poorly differentiated adenocarcinomas with one signet ring cell carcinoma in 5 mice of group 2 and one well differentiated adenocarcinoma in group 3. In the forestomach, only one squamous cell carcinoma was found at week 54 in group 1 along with a single well differentiated adenocarcinoma in the duodenum. Thus, MNU in the drinking water selectively induced neoplastic lesions in the glandular stomach epithelium of mice.

The carcinogenic potential of 1-hydroxyanthraquinone (HA), a naturally occurring compound, was examined. A total of 60 male ACI/N rats, 1.5 months old at the commencement were divided into two groups. Group 1 (30 rats) were fed the diet containing HA at a concentration of 1% throughout the experiment (480 days). Group 2 (30 rats) served as the control given a basal diet alone. Twenty-five of 29 effective animals in group 1 developed adenomas or adenocarcinomas in the cecum or upper portion of the colon, the mean number of large bowel tumors/tumor bearing rat being 2.3. In addition to these intestinal tumors, liver neoplasms (neoplastic nodules and hepatocellular carcinomas) were observed in 12 rats and benign stomach tumors were obtained in five animals; no rats of group 2 demonstrating development of any of these tumor types. The incidences of the large bowel, liver and stomach neoplasms in group 1 were all significant as compared with group 2 (P less than 2 x 10(-13), P less than 5 x 10(-5) and P less than 3 x 10(-2) respectively) clearly indicating that HA is carcinogenic in rats.

Brain arteriovenous malformations are considered to originate from a congenital maldevelopment of the brain vessels. Although there have been occasional reports suggesting a familial incidence of these lesions, data for only 10 families have been accumulated in the literature. The authors report on six such cases in three families. This high rate of occurrence of familial cases suggests an involvement of genetic factors.