Inhibition of 7,12-dimethylbenz[a]anthracene-induced genotoxicity in Chinese hamster ovary cells by retinol and retinoic acid.

Abstract:

:The effects of retinol and retinoic acid on cytotoxicity and mutation expression at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in Chinese hamster ovary (CHO) cells with or without exogenous metabolic activation were studied in the presence and absence of known chemical mutagens. Neither retinol nor retinoic acid induced mutants at the HGPRT locus of CHO cells at concentrations ranging from 1 microM to 50 microM without exogenous metabolic activation, and at concentrations ranging from 1 microM to 25 microM in the presence of Aroclor 1254-induced rat liver S9. Retinol and retinoic acid did not affect 100 micrograms/ml ethyl methanesulfonate-induced cytotoxicity or mutations at the HGPRT locus of CHO cells in the absence of exogenous metabolic activation at concentrations ranging from 1 microM to 25 microM. In contrast, retinol and retinoic acid inhibited 7,12-dimethylbenz[a]anthracene-induced cytotoxicity and mutation induction at the HGPRT locus of CHO cells when either uninduced Sprague-Dawley rat liver S9, Aroclor 1254-induced Sprague-Dawley rat liver S9 or co-cultivated primary Sprague-Dawley rat hepatocytes were used to provide metabolic activation. These data show that retinoids are capable of inhibiting mutation induction in mammalian cells in vitro by a chemical promutagen requiring metabolic activation to a reactive form, and suggest that such inhibition is due to an alteration of mutagen metabolism.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Budroe JD,Schol HM,Shaddock JG,Casciano DA

doi

10.1093/carcin/9.7.1307

subject

Has Abstract

pub_date

1988-07-01 00:00:00

pages

1307-11

issue

7

eissn

0143-3334

issn

1460-2180

journal_volume

9

pub_type

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