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PMID: 106390 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Single-step selection of clones of a mouse hepatoma line deficient in aryl hydrocarbon hydroxylase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 76 ·No. 1 ·1979-01-00 ·Pages 373-6

Hankinson O

Abstract

The mouse hepatoma line Hepa-1 has high and inducible aryl hydrocarbon (benzo[a]pyrene) hydroxylase[benzo[a]pyrene, reduced-flavoprotein:oxygen oxidoreductase (3-hydroxylating), EC 1.14.14.2] activity. Fourteen subclones of a clonal derivative of Hepa-1 were isolated and shown not to display heterogeneity in aryl hydrocarbon hydroxylase activity beyond what could be ascribed to experimental error. Hepa-1 was found to be very sensitive to benzo[a]pyrene (BaP) toxicity and a single-step selection procedure for isolating clones resistant to BaP at 4 microgram/ml was designed. Those BaP-resistant variants tested had much reduced aryl hydrocarbon hydroxylase activities under both inducing and noninducing conditions and they retained their resistance to BaP and low aryl hydrocarbon hydroxylase activities over considerable periods of time of culture in the absence of BaP. The spontaneous rate of origin of the BaP-resistant clones was estimated, by Luria-Delbrück fluctuation analysis, to be 2 X 10(-7) events per cell per generation. It is concluded that the properties of the variants are consistent with the notion that they are mutational in origin and that this system is a promising one for carrying out a somatic cell genetic analysis of aryl hydrocarbon hydroxylase.

MeSH Terms
9,10-Dimethyl-1,2-benzanthracene/pharmacology Animals Aryl Hydrocarbon Hydroxylases/deficiency,genetics Benzopyrenes/pharmacology Cell Separation/methods Clone Cells/enzymology Drug Resistance Liver Neoplasms, Experimental/enzymology Mice Mutation Selection, Genetic
Chemicals
Benzopyrenes 9,10-Dimethyl-1,2-benzanthracene Aryl Hydrocarbon Hydroxylases
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Hankinson O
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27 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.76.1.373
Published
1979-01-00
Pages
373-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC382941
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.76.1.373 PMC Full Text View journal details
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