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Abstract

In the context of a general study on the regulation of proliferation in mammalian cell populations during carcinogenesis, DNA synthesis and proliferative activity in rat liver was investigated during carcinogenesis by continuous administration of diethylnitrosamine. This carcinogenic system is characterised by an extremely high and liver specific tumour yield and very precise dose response relationships (median time of death with multifocal hepatocellular carcinomata: 160 days±6% S.D.). Autoradiographic determination of ³H-thymidine labelling indices (L.I.) after in vivo pulse exposure to ³H-Tdr at several stages of carcinogenesis was combined with in vitro measurements of ³H-Tdr incorporation into fresh liver explants under standardised conditions. Whereas the proliferative activities of the non-parenchymal cell populations remained unaltered during carcinogenesis, 3H-Tdr incorporation and L.I. of the parenchymal cell population showed characteristic changes. These are analysed and discussed in relation to the interference of the carcinogen with mechanisms controlling liver cell proliferation.