Studies of the repair of O/sup 6/-alkylguanine and O/sup 4/-alkylthymine in DNA by alkyltransferases from mammalian cells and bacteria

Journal Article · Tue Oct 01 04:00:00 EDT 1985 · Environ. Health Perspect.; (United States)

DOI:https://doi.org/10.1289/ehp.8562109· OSTI ID:5317128

Pegg, A E; Dolan, M E; Acchitano, D; Morimoto, K

O/sup 6/-Methylguanine in DNA is repaired by the action of a protein termed O/sup 6/-alkylguanine-DNA alkyltransferase (AT) which transfers the methyl group to a cysteine residue in its own sequence. Since the cysteine which is methylated is not regenerated rapidly, if at all, the capacity for repair of O/sup 6/-methylguanine is limited by the number of molecules of the AT available within the cell. The level and inducibility of the AT differed greatly in different mammalian cell types and species with the highest levels in human tissues and in liver and the lowest levels in brain. In E. coli such exposure increased the activity more than 100-fold. The protein isolated from E. coli removed methyl groups much more rapidly than the larger alkyl groups but the mammalian AT isolated from rat liver showed much less difference in rate with adducts of different size. Ethyl and n-propyl groups were removed by the rat liver AT only three to four times more slowly than methyl groups. Another important difference between the bacterial and mammalian ATs is that the bacterial protein was also able to remove methyl groups from the O/sup 4/-position of thymine in methylated DNA or poly(dT) but the AT from rat liver or human fibroblasts did not repair O/sup 4/-methylthymidine. These results indicate that the results obtained with the E. coli system may not be a suitable model for extrapolation to predictions of the effects of alkylating agents in initiating tumors or mutations in mammalian cells.

• Research Organization: Pennsylvania State Univ. College of Medicine, Hershey
• OSTI ID: 5317128
• Journal Information: Environ. Health Perspect.; (United States), Journal Name: Environ. Health Perspect.; (United States) Vol. 62; ISSN EVHPA
• Country of Publication: United States
• Language: English

Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
560302 -- Chemicals Metabolism & Toxicology-- Microorganisms-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATING AGENTS
AMINES
ANIMAL CELLS
AROMATICS
AZAARENES
AZINES
BACTERIA
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
DIGESTIVE SYSTEM
ENZYME ACTIVITY
ENZYMES
ESCHERICHIA COLI
GLANDS
GUANINE
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
LABELLED COMPOUNDS
LIVER
MICROORGANISMS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PURINES
PYRIMIDINES
RECOVERY
REPAIR
TRANSFERASES
TRITIUM COMPOUNDS
URACILS