COMPARISON OF 2-STAGE EPIDERMAL CARCINOGENESIS INITIATED BY 7,12-DIMETHYLBENZ(A)ANTHRACENE OR N-METHYL-N'-NITRO-N-NITROSOGUANIDINE IN NEWBORN AND ADULT SENCAR AND BALB-C MICE
To define factors which determine susceptibility to chemical carcinogenesis, mice sensitive (SENCAR) and resistant (BALB/c) to epidermal carcinogenesis were studied under several treatment conditions for sensitivity to initiation by 7,12-dimethylbenz(a)anthracene [DMBA] or N-methyl-N''-nitro-N-nitrosoguanidine and promotion by 12-O-tetradecanoylphorbol-13-acetate [TPA]. In newborns of both strains, topical application of initiator was much less effective than in adults. Initiation by i.p. injection of DMBA is at least as effective in newborns as in adults, which may indicate that topically applied carcinogen is not delivered effectively to target cells in newborns. Thus, newborn epidermis can respond to cells in newborns. Thus, newborn epidermis can respond to DMBA as well as adult epidermis when the initiator is appropriately administered. SENCAR mice are much more sensitive than are BALB/c mice to both initiators, which suggests that enhanced metabolic activation of hydrocarbon carcinogens by SENCAR mice is unlikely to account for their sensitivity. Newborn male SENCAR mice developed .apprx. 50% more papillomas than did females in all groups. BALB/c newborn mice developed so few tumors that a meaningful comparison of sensitivity of males and females could not be made. The increased sensitivity of SENCAR mice was apparent regardless of administration route of initiator or the age or sex of the mice. SENCAR mice also developed a significant number of papillomas and squamous cell carcinomas with TPA promotion in the absence of an exogenous initiator. The skin of SENCAR mice may contain an initiated population of cells capable of responding to tumor promoters.