NDLI: Phenotypic evolution of cells resistant to bromodeoxyuridine.

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Phenotypic evolution of cells resistant to bromodeoxyuridine.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Harris, M. Collier, K.
Abstract	Variants resistant to bromodeoxyuridine (BrdUrd) and deficient in thymidine kinase (ATP:thymidine 5'-phosphotransferase; EC 2.7.1.21) have been obtained from V79 Chinese hamster cells by a combination of spontaneous and drug-induced change. Initial mutations take place in wild-type populations as a facilitating step to give partially resistant clones that can be isolated by one-step selection in BrdUrd. When these tolerant populations are maintained for extended periods in BrdUrd-containing medium, a gradual phenotypic transition occurs in which BrdUrd appears to act as an inductive as well as selective agent. Thymidine kinase activity declines logarithmically over an interval of 8-10 weeks as the growth rate rises and the cells become completely resistant to BrdUrd. Relative plating efficiency in hypoxanthine/aminopterin/thymidine medium also decreases, but the decrease is not coordinate with shifts in thymidine kinase activity. The potential for colony formation in hypoxanthine/aminopterin/thymidine continues to decrease exponentially for at least 18 weeks after thymidine kinase deficiency and complete resistance to BrdUrd have been established. These phenotypic modifications are continuous or multistep in character; by clonal analysis they are found to occur in most, if not all, cells maintained in the presence of BrdUrd. Populations in transition thus come to be complex mosaics of different phenotypes that are comparatively stable if isolated in drug-free medium. The progressive evolution of cells resistant to BrdUrd will require new models for an underlying explanation.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	7
Volume Number	77
Language	English
Publisher	National Academy of Sciences
Publisher Date	1980-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Bromodeoxyuridine Pharmacology Drug Resistance Thymidine Kinase Genetics Animals Biological Evolution Clone Cells Physiology Cricetinae Cricetulus Mutation Phenotype Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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