Enzymology of repair of DNA adducts produced by N-nitroso compounds
The biological effects of DNA adducts depend on their nature, and on their half-lives relative to the rates of DNA replication and transcription. Their half-lives are determined by the rates of spontaneous decay, such as depurination, and the rates of enzymatic repair of the adducts or their decay products. The principle modes of repair of methylating and ethylating agents are by glycosylase catalyzed depurination of 7-alkylguanine and 3-alkyladenine and by the dealkalation of O/sup 6/-alkylguanine. Repair by dealkylation cannot be detected by the standard methods used to measure DNA repair, but it is easy to estimate the acceptor activity in cell extracts by measuring the transfer of radioactive O/sup 6/-alkyl groups in an exogenous DNA to protein. In extracts of cells treated with alkylating agents the activity is depressed because the endogenous DNA is rapidly dealkylated, using up the acceptor activity. In many cell types the decrease in activity is followed by an increase to the normal constitutive level. In other cells there is no such adaptive response. Differences in constitutive levels of methyl accepting activity in extracts of human lymphocytes and on the acceptor activity in lung macrophages from smokers (low activity) and non-smokers (high activity) have been observed. 46 references.
- Research Organization:
- Brookhaven National Lab., Upton, NY (USA)
- DOE Contract Number:
- AC02-76CH00016
- OSTI ID:
- 5814067
- Report Number(s):
- BNL-33557; CONF-8309146-1; ON: DE83017981
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ALKYLATING AGENTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL HALF-LIFE
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
DNA
ENZYME ACTIVITY
KINETICS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
REACTION KINETICS
RECOVERY
REPAIR