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.
Skinner
M A
MA
Ho
H J
HJ
Chan
V L
VL
D000241:Adenosine / Q000494:pharmacology* / Q000633:toxicity; D000248:Adenosine Kinase / Q000502:physiology; D000818:Animals; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008745:Methylation; D009154:Mutation; D012343:RNA, Transfer / Q000378:metabolism*
D004247:DNA; D012343:RNA, Transfer; D000248:Adenosine Kinase; D000241:Adenosine