Multiple etiologic factors in neoplastic development.

The detailed analysis of mammary neoplasia in inbred mice has disclosed 3 important etiologic factors, compris ing, as stated in Bittner's 3-factor hypothesis, a genetic factor, a hormonal factor, and a milk-borne tumor agent with the properties of a virus and now usually called the milk agent or the Bittner virus. Within certain limits, an excess of one factor can compensate for deficiency in another, but ordinarily, to ensure a high and early mci dence of mammary tumors, the 3 factors must act co operatively. i\Iammary neoplasia develops spontaneously and can be induced experimentally by administering car This paper is concerned primarily with the multiplicity of factors, acting simultaneously or consecutively, that are implicated in the development of individual tumors. The most conspicuous primary inductive or causative mech anisms of carcinogenesis, as revealed by experimental analysis, do not necessarily provide the best clues to practicable measures of prophylaxis and therapy in man. The present discussion therefore is not restricted to the actions of proved carcinogens but extended to the varied factors both carcinogenic and noncarcinogenic that to a significant degree influence the initiation of neoplasia and its subsequent course. The title applies most directly to the multiple factors that act cooperatively to induce a particular kind of neoplasia in a single individual. The