A single injection of
dimethylnitrosamine (DMN) given to adult rats induces
hepatocellular carcinoma if given during the period of restorative
hyperplasia following partial
hepatectomy. The effect of DMN on the sequence of biochemical events in regenerating liver is therefore of interest. As
carcinogenesis is likely to involve a change in control of gene expression, and as evidence suggests that
non-histone chromosomal proteins (NHP) are involved in gene control, the effect of DMN on synthesis of NHP in regenerating liver was studied. A well-defined group of NHP, the high mobility group (HMG), known to be specifically associated with
DNA active in transcription, were investigated. Partial
hepatectomy was found to cause a large increase in incorporation of [3H]
lysine into
HMG proteins; this did not occur immediately, but was apparent at the time of
DNA synthesis and of mitosis. DMN did not alter the relative amounts of different
HMG proteins in relation to
histone H1, but the
carcinogen caused a considerable reduction in incorporation of [3H]
lysine. This decreased synthesis of the
proteins which may function as gene derepressors may well be relevant in
carcinogenesis.