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Inhibition of DNA methylation by chemical carcinogens in vitro.

Abstract：

:A diverse range of ultimate chemical carcinogens inhibited the transfer of methyl groups from S-adenosylmethionine to hemimethylated DNA in a reaction catalyzed by mouse spleen methyltransferase. The formation of alkali-labile sites in DNA lessened its ability to accept methyl groups in vitro, but the methylation reaction was much less sensitive to thymine dimers or double-strand breaks. Carcinogens induced the formation of alkali-labile DNA lesions, but the degree of methyltransferase inhibition observed was greater than that expected for this damage alone. Certain carcinogens were also capable of direct modification and inactivation of the methyltransferase enzyme. Benzo(a)pyrene treatment of living BALB/3T3 A31 clone 1-13 but not C3H/10T1/2 clone 8 cells resulted in a 12% decrease in total 5-methylcytosine content of cellular DNA. Carcinogenic agents may therefore cause heritable changes in 5-methylcytosine patterns in certain cell types by a variety of mechanisms, including adduct formation, induction of apurinic sites and single-strand breaks and direct inactivation of DNA methyltransferase.

journal_name

Cell

journal_title

Cell

authors

Wilson VL,Jones PA

doi

10.1016/0092-8674(83)90514-7

subject

Has Abstract

pub_date

1983-01-01 00:00:00

pages

239-46

issue

1

eissn

0092-8674

issn

1097-4172

pii

0092-8674(83)90514-7

journal_volume

32

pub_type

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