The action of rat cytosol enzymes on some methylated nucleic acid components produced by the carcinogenic N-nitroso compounds.

Abstract

The stabilities of several alkylated nucleic acid components have been examined in the presence of cytosol extracts from a variety of rat tissues. An activity capable of demethylating O6-methyldeoxyguanosine was readily detectable in all tissues examined; arranged in approximate order of decreasing specific activity these are as follows: small intestine, spleen, kidney, lung, liver, skin, heart and brain. The in vitro requirements for the activity derived from liver and the observations that O6-methylguanine and its deoxynucleoside 5'-monophosphate are insensitive to the action of these extracts suggests that this activity may be due to an enzyme which resembles adenosine deaminase. In contrast to the ready degradation of O6-methyldeoxyguanosine the corresponding ethyl derivative was degraded very much more slowly but there was no evidence for other activities against the O4- and O2-methyldeoxythymidines. Similarly, no demethylation of the N-substituted deoxynucleosides, 3-methyldeoxycytidine 3-methldeoxythymidine, 1-methyldeoxyadenosine and 7-methyldeoxyguanosine, was detected.