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PMID: 6178113 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Induction of prolactin-deficient variants of GH3 rat pituitary tumor cells by ethyl methanesulfonate: reversion by 5-azacytidine, a DNA methylation inhibitor.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 79 ·No. 9 ·1982-05-00 ·Pages 2967-70

Ivarie RD, Morris JA

Abstract

GH3 cells are a rat pituitary tumor line expressing two pituitary peptide hormones, prolactin (rPRL) and growth hormone. Recently, it was found that the DNA alkylating agent ethyl methanesulfonate can induce the appearance of rPRL-deficient GH3 cell variants at a high frequency (ca. 20-30%). As shown here, such variants cannot be induced at high frequency by irradiation of wild-type GH3 cells with ultraviolet light, indicating that the effect may be specific to treatment with alkylating agents. Furthermore, the DNA methylation inhibitor 5-azacytidine reverted an ethyl methanesulfonate-induced rPRL-deficient variant into rPRL-expressing cells at high frequency (ca. 50%). The revertants were stable for at least 30-35 generations. These results support the hypothesis that the alkylating agent may promote the specific methylation of the rPRL gene or a gene regulating its activity, either one of which leads to inactivation of expression of the rPRL gene in GH3 cells.

MeSH Terms
Animals Azacitidine/pharmacology Cell Line Ethyl Methanesulfonate/antagonists & inhibitors Gene Expression Regulation/drug effects Methylation Mutation/drug effects Phenotype Pituitary Neoplasms/metabolism Prolactin/deficiency,genetics Rats Ultraviolet Rays
Chemicals
Prolactin Ethyl Methanesulfonate Azacitidine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ivarie R D
Morris J A
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52 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.79.9.2967
Published
1982-05-00
Pages
2967-70
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC346329
Subset
IM
Grants
NCI NIH HHS · CA-28826 · United States
External Links
PubMed source DOI: 10.1073/pnas.79.9.2967 PMC Full Text View journal details
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