Decreased methylation rates of DNA in SV40‐transformed human fibroblasts

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.