Inhibition of methylation of DNA and tRNA by adenosine in an adenosine-sensitive mutant of the baby hamster kidney cell line.

An adenosine-sensitive (Ados) mutant of baby hamster kidney (BHK) cells, ara-S10d, when treated with a toxic concentration of adenosine (Ado), displayed a substantial elevation of S-adenosylhomocysteine (SAH), S-adenosylmethionine (SAM), and methylthioadenosine (MTA). Wild-type BHK cells treated with the same concentration of Ado (not toxic to these parental cells) produced an elevation of SAH 1.5 times higher than that of ara-S10d cells without a concurrent elevation of SAM or MTA. Inhibition of methylation of DNA and tRNA is greater in ara-S10d cells treated with Ado than that of similarly treated wild-type cells. This inhibition was correlated with the enhanced Ado toxicity, suggesting inhibition of methylation as a possible causal factor for the great increase in Ado sensitivity. Inhibition of methylation may be due to the elevated level of MTA and not solely to the elevation of SAH, a well-known potent inhibitor of numerous methyltransferases.