1986
DOI: 10.1128/mcb.6.9.3023
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Genomic hypomethylation and far-5' sequence alterations are associated with carcinogen-induced activation of the hamster thymidine kinase gene.

Abstract: We have investigated the mechanism of activation of an inactive but functionally intact hamster thymidine kinase (TK) gene by the chemical carcinogen N-methyl-N'-nitro-N-nitrosoguanidine. Following carcinogen treatment of TK-RJK92 Chinese hamster cells, aminopterin-resistant (HAT') colonies appeared at a frequency 50-fold higher than in untreated controls. More than 80% of these HATr variants expressed TK enzymatic activity and were divided into high-abd low-activity classes. In all TK+ variants, TK expression… Show more

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Cited by 22 publications
(19 citation statements)
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“…Line 15 is an aminopterinresistant TK+ clone isolated following N-methyl-N'-nitro-Nnitrosoguanidine treatment of the aminopterin-sensitive TKChinese hamster fibroblast cell line RJK92 (9). The hamster cell lines (line 15, RJK92, and TK+ V79) were grown as described (9).…”
Section: Methodsmentioning
confidence: 99%
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“…Line 15 is an aminopterinresistant TK+ clone isolated following N-methyl-N'-nitro-Nnitrosoguanidine treatment of the aminopterin-sensitive TKChinese hamster fibroblast cell line RJK92 (9). The hamster cell lines (line 15, RJK92, and TK+ V79) were grown as described (9).…”
Section: Methodsmentioning
confidence: 99%
“…Line 15 is an aminopterinresistant TK+ clone isolated following N-methyl-N'-nitro-Nnitrosoguanidine treatment of the aminopterin-sensitive TKChinese hamster fibroblast cell line RJK92 (9). The hamster cell lines (line 15, RJK92, and TK+ V79) were grown as described (9). For conventional gel electrophoresis and inverse PCR template construction, genomic DNA was isolated by proteinase K/SDS and RNase A digestion and organic extraction (12).…”
Section: Methodsmentioning
confidence: 99%
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“…Methylation patterns can also be altered by drug exposure. Sites in the 5' region of the hamster TK gene became unmethylated in MNNG induced revertants of TK-cells (Barr et al, 1986). In addition structural rearrangements, either spontaneous or drug induced, may bring genes into proximity with new regulatory elements which act on gene promotors or may modify the binding of sequence specific regulatory elements by altering chromatin structure.…”
mentioning
confidence: 99%