The rates of methylation of total cellular DNA and newly synthesized DNA were measured in four unrelated SV40-transformed human fibroblast lines and in four control parent fibroblast lines. Rates of methylation of total cellular DNA were decreased by a factor of 1.8-2.3 in the transformed cells relative to control cells. Methylation was largely (75%-87%) restricted to newly synthesized DNA in control and transformed fibroblasts, and methylation rates of newly synthesized DNA were diminished in transformed cells by 12-to 19-fold relative to control cells. Growth rates were similar in the normal and transformed cells. The cellular uptake of methionine and conversion to S-adenosylmethionine were similar in the normal and transformed cells, suggesting no major differences between the normal and transformed cells in the cellular transport of methionine, methionine S-adenosyltransferase activity, or the intracellular concentrations of methionine and S-adenosylmethionine. The diminished rates of DNA methylation that we have observed suggest a possible mechanism for altered gene expression and growth control in transformed cells.
Cancer 57:764-768, 1986.
OLYOMA and SV40 virus-transformed human cell P lines demonstrate many aberrations in growth control and provide a model for the study of events governing the spontaneous development of malignant tumors in animals and humans. ' ,* The molecular events underlying eukaryotic cellular transformation have yet to be fully elucidated. Recently, considerable evidence has accumulated that DNA methylation is involved in the control of gene expression; specific demethylation events, for example, appear to be required for gene expression during development and differentiati~n.~.~ Methylation of base residues in DNA appears to correlate with gene inactivity, while increased gene expression is associated with DNA hypomethylation and has been observed in the globin gene,'x6 the ovalbumin gene7 and several viral genes.8 Ab-