STAGES OF INITIATION AND PROMOTION IN HUMAN CARCINOGENESIS

27 May

Evidence for the existence of the stages of initiation and promotion in the human have come largely from clinicopathological  and epidemiological  studies. That initiation occurs in the hu- man is evidenced by the spontaneous  incidence of cancer in the human population,  implying initiation as an essential component for the development  of such neoplasms. Evidence for the existence of the stage of promotion in human neoplasia is not so definitive as that seen in the animal, but since the pathogenesis of cancer development in the human may be recapitulated in the animal, one may use such model systems to potentially identify the stage of promotion in the development of human neoplasia.

Morphological evidence for the clonal expansion of initiated cells during tumor promotion is based on the description  of preneoplastic  lesions and attempts to relate such lesions to the development of specific malignancies (cf. Henson and Albores-Saavedra, 1986; Dunham, 1972). Table 7.11 lists some preneoplastic lesions of the human and their related or analogous lesions in the rodent. The preneoplastic  nature of the human lesions has been inferred from both histo- pathological and epidemiological studies. The similarity of putative human preneoplastic lesions to comparable  lesions known to be preneoplastic  that develop in experimental  animal models further supports the preneoplastic nature of the human alterations. For example, nodular hyper- plasia of the adrenal cortex is quite commonly seen in the rodent, and the preneoplastic potential of the lesions has been implied for many years in the animal (Dunn, 1970). The lesions observed in mammary  carcinogenesis  are also quite analogous  in animals and humans (van Bogaert,1984). In addition, the lesions observed in the liver and colon of animals are strikingly similar to their human counterparts. Although examples exist where the congruence of the preneoplastic counterpart in the human is not distinct during pathogenesis of the developing neoplasm in ani- mals (e.g., the dysplastic nevus to malignant melanoma), in general the similarities of preneo- plastic lesions in the human and experimental  animal strongly  argue that the stages of the carcinogenic process in mammals are very similar across species.

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