Abstract
CELL proliferation has often been implicated in the development of cancer with chemicals1–3. Supportive evidence for this is the observation that several carcinogens that normally do not induce liver cancer in intact adult animals, especially with a single dose, become carcinogenic if administered as a single injection after partial hepatectomy (PH)1. In these conditions, it is thought that PH may act during initiation, presumably by fixation of some carcinogen-induced DNA damage through replication of the altered DNA. However, because carcinogenesis is a multi-step process, often involving the appearance of several new cell populations between the initial target cells and the ultimate cancer4,5, it is possible that the regenerative response of liver following PH could have a major effect on one or more steps subsequent to initiation. Thus, the use of a very late end-point (cancer) makes it difficult, if not impossible, to relate with any accuracy some very early event to any specific step in the carcinogenic process. Solt and Farber6 have recently developed a new approach to the sequential analysis of carcinogenesis in vivo that delineates the first few steps in the process and is a quantitative assay for initiation of liver cancer. We have used this model to investigate whether cell replication exerts its first effect on initiation or on some later step in the carcinogenic process. And if initiation is at least one site of action, when in the regenerative cell cycle is a carcinogen most effective and what biochemical events might be involved at this phase of the cell cycle?
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CAYAMA, E., TSUDA, H., SARMA, D. et al. Initiation of chemical carcinogenesis requires cell proliferation. Nature 275, 60–62 (1978). https://doi.org/10.1038/275060a0
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DOI: https://doi.org/10.1038/275060a0
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