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Methylation of deoxycytidine in replicating cells treated with ultraviolet radiation and chemical carcinogens

Journal Article · · Carcinogenesis (N.Y.); (United States)

5-Methyl-2'-deoxycytidine (m5dC) levels were measured in DNA from three types of cultured cells following treatment with u.v. radiation and two chemical carcinogens, N-methyl-N-nitrosourea (MNU) and N-acetoxy-2-acetylaminofluorene (NA-AAF). Control values for m5dC in Raji cells (a human lymphoblastoid cell line), S49 cells (a mouse thymic lymphoma cell line) and human diploid fibroblasts are 3.6%, 3.6% and 3.2%, respectively. None of the damaging agents produced a detectable change in methylation levels of newly replicated DNA, even at levels of damage that inhibited replication by 95%. In contrast, treatment with 5-aza-2'-deoxycytidine, a known methyltransferase inhibitor, transiently reduced genomic methylation by 89% and 74% in Raji and S49 cells, respectively. Although other investigators have found a marked reduction in m5dC in DNA replicated after carcinogen treatment, our experiments indicate that extensive demethylation is not a necessary consequence of DNA damage.

Research Organization:
Washington University School of Medicine, Department of Pathology, St. Louis, MO
OSTI ID:
6440369
Journal Information:
Carcinogenesis (N.Y.); (United States), Journal Name: Carcinogenesis (N.Y.); (United States) Vol. 5:9; ISSN CRNGD
Country of Publication:
United States
Language:
English