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Modulation of ultraviolet light‐, ethyl methanesulfonate‐, and 7, 12‐dimethylbenz[a]anthracene‐induced unscheduled dna synthesis by retinol and retinoic acid in the primary rat hepatocyte
Author(s) -
Budroe John D.,
Shaddock Joseph G.,
Casciano Daniel A.
Publication year - 1987
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.2850100203
Subject(s) - retinoic acid , 7,12 dimethylbenz[a]anthracene , hepatocyte , ethyl methanesulfonate , methyl methanesulfonate , retinol , chemistry , ultraviolet light , retinoic acid inducible orphan g protein coupled receptor , ultraviolet radiation , biochemistry , biology , dna , retinoid , dna damage , mutation , photochemistry , gene , radiochemistry , vitamin , carcinogenesis , in vitro , dmba
The effects of retinol and retinoic acid on unscheduled DNA synthesis (UDS) in primary Sprague‐Dawley rat hepatocytes were studied in the presence and absence of known chemical and physical mutagens. Neither retinol nor retinoic acid caused a significant increase in UDS over solvent control at concentrations ranging from 1 μM to 50 μM. Retinol and retinoic acid did not significantly affect 200 μg/mL ethyl methanesulfonate(EMS)‐ or 32 J/m 2 ultraviolet light(UV)‐induced UDS at concentrations ranging from 1 μM to 50 μM. In contrast, retinol and retinoic acid significantly inhibited 2.5 μg/mL and 5.0 μg/mL 7,12‐dimethyl‐benz[a]anthracene(DMBA)‐induced UDS at concentrations of 1 μM or greater. Retinol‐and retinoic acid‐induced hepatocytotoxicity was studied in vitro using lactate dehydrogenase (LDH) release as an indicator of cytoxicity. Neither retinol nor retinoic acid caused significant increases in LDH release over solvent control 3 hours after treatment, whereas retinol caused a biologically significant increase in LDH release 24 hours posttreatment at concentrations of 50 μM and 100 μM. These data suggest that nontoxic concentrations of retinol and retinoic acid do not inhibit the DNA excision repair process but apparently affect the effective DNA adduct load due to the ultimate species of DMBA metabolite responsible for hepatocellular DNA damage.