Two animal models have proved to be particularly promising for study of modulating processes in chemical carcinogenesis. In the first, athymic nude (nu/nu) mice and their normal, hairy counterparts (nu/+) were subjected to a variety of procedures known to result in tumor formation with normal mouse skin. The study revealed, for the first time, that nudes are more sensitive than normal to causation of squamous skin tumors. This was true of a variety of chemical and physical causative agents, including dimethylbenzanthracene (DMBA) as initiator and 12-0-tetradecanoylphorbol-13-acetate (TPA) as a promoter, repeated treatment with methylnitrosourea (MNU), a single dose of MNU followed by TPA, intraperitoneal ethylnitrosourea followed by TPA, or repeated exposure to ultraviolet light. These protocols may now be used to study the special properties of nude skin and/or lack of immune surveillance as determining factors in sensitivity to carcinogenesis. Furthermore, the DMBA treatment resulted in a high incidence of sebaceous adenomas, which were frequently overlaid by hyperplastic epidermis and sometimes squamous papillomas, providing a model for study of local cellular interactions in tumorigenesis. In the second project, the role of induction of enzymes metabolizing chemical carcinogens in susceptibility to tumorigenesis was investigated by use of 6 mouse strains of varying inducibility, including inbred C57BL/6, BALB/c, and C3H (inbred, highly inducible), noninbred Swiss (moderately inducible), and DBA and AKR (noninducible). Females of each strain were given the carcinogen, methylcholanthrene (MC), i.e., with or without prior exposure to the enzyme inducer beta-naphtho flavone (beta-NF). The beta-NF pretreatment protected against mortality due to MC-caused malignancy and specific tumor types, including those of lung, forestomach, mammae, mesothelium, and lymphoid and connective tissue by 50-100% in the induction-responsive strains, whereas in the DBA mice the only effect was a moderate reduction in lymphomas. There was no effect in the AKRs. This confirmation of the protective potential of induction of carcinogen detoxification pathways could be of potential public health usefulness.
