NDLI: HeLa cell variants that differ in sensitivity to monofunctional alkylating agents, with independence of cytotoxic and mutagenic responses.

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HeLa cell variants that differ in sensitivity to monofunctional alkylating agents, with independence of cytotoxic and mutagenic responses.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Spencer, L. A. Baker, R. M. Van Voorhis, W. C.
Abstract	Different strains of the established human cell line HeLa differ substantially in sensitivity to ethyl methanesulfonate (EtMes). The EtMes doses effective for either cytotoxicity or mutation induction in a line of HeLa S3 cells are about 1/10th those required in the CCL2 HeLa line of the American Type Culture Collection. By plating the sensitive HeLa S3 line in the presence of highly cytotoxic doses of EtMes, we obtained a clone (designated A6) that displays about 7-fold greater resistance to EtMes toxicity. This A6 isolate is also cross resistant to other simple monofunctional alkylating agents-exhibiting about 4-fold increased resistance to methyl methanesulfonate and 10- to 15-fold increased resistance to N-methyl-N'-nitro-N-nitrosoguanidine but is similar to the S3 parent in sensitivity to mitomycin C, UV radiation, and gamma-rays. In contrast to the results for cytotoxicity, the A6 variant and the S3 parent showed the same high susceptibility to EtMes induction of ouabain-resistant mutations. This is direct biological evidence that different alkylation lesions are normally responsible for mutagenic and cytotoxic effects. The S3 and A6 cell lines may differ in DNA repair capability specific to certain potentially lethal alkylation products. The comparative sensitivity of the A6 cells to alkylation mutagenesis may also prove useful in cell genetic studies by facilitating the generation of multiple mutants for recessive alleles and permitting exceptionally sensitive detection of specific mutagenic effects.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	10
Volume Number	76
Language	English
Publisher	National Academy of Sciences
Publisher Date	1979-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Ethyl Methanesulfonate Pharmacology Genetic Variation HeLa Cells Physiopathology Mutation Drug Effects Cell Survival Drug Resistance Mitomycins Ouabain Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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