Reversible and irreversible lesions in processes of cancer development

Most known carcinogenic processes consist of a multistep sequence in which new cell populations are the links in the chain of events triggered by the chemical carcinogen. Although the later steps are self-generating, in that they require no obvious external stimulus, the early steps are very much environment-dependent. Initiation of chemical carcinogenesis appears to consist of at least two steps, a reversible biochemical one and a round of cell proliferation which results in the generation of a relatively permanent, irreversible rare event, the promotion of initiated cells. The selection of these cells - promotion - is largely reversible, with only an occasional selected focal area of proliferation persisting to the next step, again a rare event. The selections of this and subsequent rare events are largely unknown as to their reversibility. The need to delineate each step is emphasized.