Chemical Carcinogens and Oncogenes

Abstract

Association of environmental chemicals as causative agents for cancer has been reported as early as 1761. The geographical pattern of incidence of cancer among human populations and its prevalence in individuals with specific occupations and habits has provided important clues on the etiology of the disease. Studies on the metabolism of potent chemical carcinogens in different cell types have identified active derivatives of many of these compounds and characterized the nature of their direct interactions with the cellular macromolecules. A strong correlation between the mutagenicity and carcinogenicity of large series of compounds suggested that DNA is the ultimate target of these carcinogens. More direct evidence for this concept originated from the classical DNA-mediated transfection studies identifying tumorigenic DNA sequences in chemically transformed cells which, when transferred to nontumorigenic cells resulted in the malignant transformation of recipient cells. Since these early reports we now know more regarding these oncogenic DNA sequences (“oncogenes”) and on the molecular aspects of chemical carcinogenesis and accompanying altered gene structure and gene expressions (increase, decrease, inactivation or novel expression). Numerous studies with end stage tumors or with tumor cells in cultures or with in vitro, transformed cells have identified several such ocogenic DNA sequences the cellular unmodified homologue of which are referred to as “protooncogenes”. It has been postulated that more than one of these cellular protooncogenes are involved in a stage specific fashion in the multistep carcinogenesis process. The cooperative interaction of different cellular protooncogenes activated at different stages of the DMBA-induced in vivo carcinogenesis in hamster buccal pouch epithelium will be elaborated.