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PMID: 3405220 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Effect of cycloheximide on development of methotrexate resistance of Chinese hamster ovary cells treated with inhibitors of DNA synthesis.

Molecular and cellular biology ·Vol. 8 ·No. 7 ·1988-07-00 ·Pages 2822-7

Sherwood SW, Schumacher RI, Schimke RT

Abstract

We examined the effects of 18 h of incubation of Chinese hamster ovary (CHO K1) cells with cycloheximide, hydroxyurea, and aphidicolin. Treatment of cells with cycloheximide alone at a concentration adequate to inhibit DNA synthesis to less than 10% of control was significantly less cytotoxic and clastogenic than treatment with hydroxyurea or aphidicolin, did not induce unbalanced cellular growth, and had no effect on the frequency of resistant cells in methotrexate selections compared with control cells. When combined with hydroxyurea or aphidicolin and compared with the effects of either drug alone, cycloheximide blocked the induction of unbalanced growth during drug treatment, reduced the frequency of chromosomal aberrations in recovering cell populations, and decreased cell killing. In addition, the increased frequency of methotrexate-resistant cells observed after treatment with hydroxyurea or aphidicolin was eliminated when cycloheximide was present during drug treatment.

MeSH Terms
Animals Cell Cycle Cell Line Cell Survival Chromosome Aberrations Cricetinae Cycloheximide/pharmacology DNA Replication/drug effects Drug Resistance Female Hydroxyurea/pharmacology Methotrexate Ovary/drug effects
Chemicals
Cycloheximide Hydroxyurea Methotrexate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sherwood S W
Department of Biological Sciences, Stanford University, California 94305.
Schumacher R I
Schimke R T
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33 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.8.7.2822-2827.1988
Published
1988-07-00
Pages
2822-7
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC363501
Subset
IM
Grants
NIGMS NIH HHS · GM 14931 · United States
External Links
PubMed source DOI: 10.1128/mcb.8.7.2822-2827.1988 PMC Full Text View journal details
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