To clarify the suitability of a newborn-mouse
carcinogenesis assay to detect
tumor-promoting activities of
carcinogens, the non-genotoxic
hydroquinone (HQ) and genotoxic
1,1-dimethylhydrazine (UDMH) were administered to mice during the promotion stage
after treatment with 1-methyl-1-nitrosourea (MNU) (20 mg/kg body wt, single
intraperitoneal injection) at day 9 after birth. Initiated males and females thus received either HQ at 0.8% in basal diet, or UDMH, at 20 mg/kg body wt once weekly by
subcutaneous injection, from day 14 until the end of the experiment at 30 weeks of age. Uninitiated newborn mice, given an injection of the vehicle (0.01 M
citrate buffer (pH 5.5), 20 mg/kg body wt), also received HQ or UDMH in the same way. Histopathologically, focal proliferative lesions were found in the livers of male mice and in the lungs of both male and female mice in the MNU-treated groups. HQ significantly increased the incidence and multiplicity of altered hepatocellular foci, the combined incidence of
hepatocellular adenomas and
carcinomas in males and the incidence and multiplicity of lung
adenomas and the combined incidence of lung
adenomas and
carcinomas in female mice. In addition, four out of eleven MNU + HQ-treated male mice developed lung
carcinomas, showing a significant elevation in multiplicity. UDMH also exhibited a tendency to increase the incidence and multiplicity of lung
adenomas in female mice. Thus
tumor-promoting effects of HQ or UDMH were apparently exerted in the target organs and the MNU-initiated two-stage newborn-mouse
carcinogenesis assay may be useful for detection of genotoxic or non-genotoxic carcinogenicity.