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

Journal Article · Wed Dec 31 23:00:00 EST 1986 · Environ. Mol. Mutagen.; (United States)

DOI:https://doi.org/10.1002/em.2850100203· OSTI ID:5507902

Budroe, J D; Shaddock, J G; Casciano, D A

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 microM to 50 microM. Retinol and retinoic acid did not significantly affect 200 micrograms/mL ethyl methanesulfonate(EMS)- or 32 J/m2 ultraviolet light(UV)-induced UDS at concentrations ranging from 1 microM to 50 microM. In contrast, retinol and retinoic acid significantly inhibited 2.5 micrograms/mL and 5.0 micrograms/mL 7,12-dimethyl-benz(a)anthracene(DMBA)-induced UDS at concentrations of 1 microM 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 microM and 100 microM. 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.

• Research Organization: Food and Drug Administration, Little Rock, AR
• OSTI ID: 5507902
• Journal Information: Environ. Mol. Mutagen.; (United States), Journal Name: Environ. Mol. Mutagen.; (United States) Vol. 10:2; ISSN ENMUE
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AROMATICS
BENZANTHRACENE
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CARBOXYLIC ACID ESTERS
CONDENSED AROMATICS
DNA REPAIR
ELECTROMAGNETIC RADIATION
EMS
ENZYMES
ESTERS
GENETIC EFFECTS
HEMIACETAL DEHYDROGENASES
HYDROCARBONS
LACTATE DEHYDROGENASE
LIVER CELLS
MAMMALS
MUTAGENS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXIDOREDUCTASES
RADIATIONS
RADIOSENSITIVITY EFFECTS
RATS
RECOVERY
REPAIR
RETINOIC ACID
RODENTS
SOMATIC CELLS
SULFONIC ACID ESTERS
ULTRAVIOLET RADIATION
VERTEBRATES