Carcinogenesis: A Fifty-Year Historical Perspective.

Abstract

viruses have been developed and studied. The results emphasize the importance of the interplay between the inducing agent, host factors, and other environmental factors in determining the likelihood of developing malignant tumors. The study of xeroderma pigmentosum has indicated how the inability to repair ultraviolet light induced DNA damage can markedly accelerate the carinogenic effects of UV light. The induction of cutaneous squamous cell carcinomas in mice by chemical carcinogens has represented a system in which especially important conceptual contributions have been made to our understanding of carcinogenesis in general. Such studies were among the first to indicate that cells pass through various stages in the progression to malignancy, which implies that several discrete changes may be required to convert cells from normal to malignant. These observations have provided an experimental framework in which to understand the long latency periods seen in many forms of clinical cancer, where the inducing agents usually remain unknown. Papillomaviruses represent important agents of benign cutaneous tumors which have recently been implicated in a variety of epithelial malignancies, especially certain genital neoplasms. In recent years, the focus of carcinogenesis studies has shifted to mechanistic analyses and to the contribution of specific genes to tumorigenesis. These analyses have suggested that cutaneous carinogenesis at the molecular level results after several identifiable genetic alterations have occurred in the cell. Thus model systems of cutaneous carcinogenesis, in which early studies provided strong evidence for cancer being a multistep process, are now identifying the specific genes whose alterations contribute to malignant conversion. This historically oriented review highlights these and related advances in understanding cutaneous carcinogenesis and suggests some questions that may be addressed in future studies.