Mouse skin papilloma formation by chronic dermal application of 7, 12-dimethylbenz[a] anthracene is not reduced by diet restriction

Diet restriction has repeatedly been shown to reduce the incidence of spontaneous and chemically induced tumors in rodents. However, no conclusive data are available to show whether carcinogenesis by chronic exposure to a genotoxic agent can also be retarded. In this study, diet restriction to 70% was investigated for a protective effect on the formation of skin papilloma in male NMRI mice treated twice weekly with 20 nmol 7,12-dimethylbenz(a)anthracene (DMBA). Rather surprisingly, no protection was seen. Both time of onset of papilloma formation (13 weeks in both groups) and time of 50% cumulative incidence (t50; 17.5 and 18 weeks) were similar in the unrestricted and the restricted group. In contrast, a clearly protective elTect was found in mice initiated with 100 nmol DMBA and promoted twice weekly with 2.5 nmol 12-O-tetradecanoylphorbol-13-acetate: the onset of papilloma formation increased from 7 to 11.5 weeks, the t50 was shifted from 8.5 to 19 weeks. Diet restriction, therefore, was not protective under conditions of chronic exposure to a genotoxic carcinogen. It cannot be considered a universal measure of cancer preventio