[Genetic transformation of somatic cells. VIII. The effect of the DNA methylation inhibitor 5-azacytidine on the stability of thymidine kinase-negative and -positive phenotypes of transformant clone cells].
A study was made of the effect of an DNA methylation inhibitor 5-azacytidine (azaC) on the frequency of reversion to a thymidine kinase-positive (TK+) phenotype in 5-bromodeoxy-uridine (BrdU)-resistant subclones obtained from clones of Chinese hamster cells transformed by thymidine kinase gene (tk-gene) of Herpes simplex virus type 1 (HSV1). It is shown that in 8 of 15 BrdU-resistant subclones azaC increases 2-1000-fold the frequency of reversion to TK+ phenotype. Variations in the inducibility of reversions to TK+ phenotype indicate that the DNA methylation associated with TK- phenotype affects but differently tk gene of HSV1. Cultivation of TK+ cells of transformant clones in the presence of azaC may lead to stabilization (or decrease in the rate of the loss) of TK+ phenotype, or may not influence the stability of transformant phenotype. The reaction of TK+ cells of transformant clones depends both on genetically determined rate of the loss of TK+ phenotype, and on the structure of transforming DNA introduced to cells. A conclusion is drawn that the TK- phenotype of transformant clone cells arises due to processes which are not associated with methylation of tk gene of HSV1 in spite of the fact that such a methylation may later stabilize significantly the TK- phenotype.
Glebov
O K
OK
Abramian
D S
DS
D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002472:Cell Transformation, Viral / Q000187:drug effects*; D002999:Clone Cells / Q000187:drug effects / Q000201:enzymology; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000037:antagonists & inhibitors* / Q000235:genetics; D004351:Drug Resistance; D005814:Genes, Viral; D008745:Methylation; D010641:Phenotype; D018139:Simplexvirus / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*; D014170:Transformation, Genetic / Q000187:drug effects*
D004247:DNA; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine; D001374:Azacitidine
Geneticheskaia transformatsiia somaticheskikh kletok. VIII. Vliianie ingibitora metilirovaniia DNK 5-azatsitidina na stabil'nost' negativnogo i pozitivnogo po timidinkinaze fenotipa kletok transformantnykh klonov.