The relevance of cell transformation to carcinogenesis in vivo

Despite the caveats concerning rodent as opposed to human cell transformation systems, the author concludes there are several areas in which cell transformation studies with rodent cells have shown clear relevance to carcinogenesis in vivo, especially studies of carcinogenic effects of high LET radiation, particularly dependence on dose rate. In vitro studies firmly established the generality of promotion by phorbol esters tumour promotors. Initial studies on suppression of transformation, notably by protease inhibitors, has led to the confirmation of this phenomenon in in vivo carcinogenesis; development of inhibitor preparations from natural sources suitable for long-term supplementation in human diet, is under investigation. The potential importance of these modifiers is further emphasized by mechanistic studies suggesting that radiation may initiate a large fraction of exposed cell population, and expression of transformation may be controlled to a large extent by environmental conditions including the presence of promoting or suppressing agents. Finally, cell transformation systems offer the opportunity for mechanistic studies of the initial stages of carcinogenesis. Provocative results have arisen in several areas consistent with findings in experimental animals. (author)