Relationship of benign papillomas to cancer induction in mouse skin

An analysis is presented for evaluating the potency of initiators, promoters, and carcinogens based on the number of tumors that occur as a function of dose and time when compounds are applied topically in an appropriate solvent to mouse skin. A given compound was tested as an initiator (a single dose followed by prolonged promotion), as a whole carcinogen (multiple applications for a prolonged period of time), and as a cocarcinogen (multiple applications for a prolonged period of time in combination with promotion). Compounds tested were 7,12 dimethylbenz(a)anthracene (DMBA), benzo(a)pyrene (B(a)P), 4-nitroquinoline-1-oxide (4-NQO), and betapropriolactone (BPL). The results indicated that various types of papillomas were produced in proportion to the dose applied to DMBA, B(a)P, and BPL. Certain of these papillomas were nonregressible and progressed readily to carcinomas; others regressed and did not progress to cancer. Multiple doses of DMBA and B(a)P produced carcinomas without an antecedent papilloma stage. The latter cancers were produced in proportion to the 2nd or 3rd power of applied carcinogen dose and were accelerated strongly by concomitant action of a promoter. Certain nonregressible papillomas probably represent the first step in a two or three step progression to cancer, although cancers from papillomas occur in proportion to dose.