John M. Budinger

Carcinogenic effects of intracolonic benzo[a]pyrene in β-naphthoflavone-induced mice

Benzo[a]pyrene (BP) was administered intracolonically to ICR/Ha and C57Bl/6 female mice, 1 mg/mouse, once weekly for 14 weeks. Half of the mice received beta-naphthoflavone (beta-NF, a mixed-function oxygenase inducer) i.p. 24 h prior to the BP. No colonic neoplasms were found in any of the mice after 18 months. However, the BP treatment did cause a significant increase in numbers of primary lung tumors, forestomach papillomas, mammary carcinomas, and sarcomas in one or both strains, relative to controls, and the incidence of all of these except for the sarcomas was significantly reduced by treatment with beta-NF prior to BP. Overall, the beta-NF pretreatment reduced total incidence of neoplasms by about 30% in the ICR/Ha mice and by about 60% in the C57Bl/6 mice, and did not potentiate the action of the carcinogen in any organ.

Qualitative histological differences between transplacentally- -induced lung tumors in young and aging mice.

Transplacentally-induced lung tumors arising in BALB/c mice 38-45 weeks old (late crop) were significantly larger and more invasive of the surrounding lung parenchyma than were the tumors appearing at 10-36 weeks (early crop). The late-crop tumors were also somewhat more papillary and heterogeneous. Development of the 2 crops of tumors from different cell types of origin is postulated. A specific association of lymphocytes with the pleural surfaces of some tumors was noted and this association was significantly more likely for tumors invading the parenchyma than for non-invasive ones.

N6 (Methylnitroso)adenosine: A carcinogenic nitrosamine derived from a naturally-occurring nucleoside

N6(Methylnitroso) adenosine (M6(NO)Ado) is found readily under acidic conditions by the interaction of nitrite with 6-methyladenosine, a naturally-occurring nucleoside. Swiss mice were treated with M6(NO)Ado by injection (40 mg/kg each treatment) transplacentally and then as newborns and young adults. The incidences of lymphomas, primary lung tumors, and hepatic neoplasms were significantly greater in these treated animals than in controls. These results demonstrate the tumorigenicity of M6(NO)Ado.