Co-carcinogens or modulators of carcinogenesis. New aspects of the etiology of human tumors and of the molecular mechanisms of carcinogenesis

Abstract

Within the last 10 years numerous new and typical exogenous cocarcinogens were identified chemically as well as biologically and characterized biochemically as initiation or tumor promoters. They are highly irritant diterpene esters of plant origin. Promoters of this type were recently detected also in the Euphorbiacea Croton flavens L., the multiple use of which for stimulants according to local habits was previously held responsible for the unusually high rate of esophageal cancer on Curacao. This detection confirms for the first time that in the etiology of human cancer besides solitary carcinogens (first-order carcinogenic risk factors) also cocarcinogens of the promoter type have to be considered (second-order carcinogenic risk factors). -- The active principles of the diterpene ester type are the strongest promoters known so far; they are noninitiators and nonmutagens. Of the manyfold biochemical activities of these promoters the three most actual are: the TPA molecule does not require activation by metabolic alteration, it releases very rapidly prostaglandin E2 from cellular membranes and it activates latent DNA-viral genoms.