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. Mutagen.; (United States)

OSTI ID:5337395

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 know chemical and physical mutagens. Neither retinol or retinoic acid caused a significant increase in UDS over solvent control at concentrations ranging from 1 ..mu..M to 50 ..mu..M. Retinol and retinoic acid did not significantly affect 200..mu..g/mL ethyl methanesulfonate (EMS)- or 32 J/m/sup 2/ ultraviolet light (UV)-induced UDS at concentrations ranging from 1..mu..M to 50 ..mu..M. In contrast, retinol and retinoic acid significantly inhibited 2.5 ..mu..g/mL and 5.0 ..mu..g/mL 7,12-dimethyl-benz(a)-anthracene(DMBA)-induced UDS at concentrations of 1..mu..M 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 ..mu..M and 100 ..mu..M. 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: Univ. of Arkansas for Medical Sciences, Little Rock
• OSTI ID: 5337395
• Journal Information: Environ. Mutagen.; (United States), Journal Name: Environ. Mutagen.; (United States) Vol. 10:2; ISSN ENMUD
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
560300 -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AROMATICS
BIOCHEMISTRY
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
CHEMISTRY
CONDENSED AROMATICS
DIMETHYLBENZANTHRACENE
DNA REPLICATION
ELECTROMAGNETIC RADIATION
EMS
ESTERS
GENETIC EFFECTS
GENETIC RADIATION EFFECTS
LABELLED COMPOUNDS
LIVER CELLS
MAMMALS
MUTAGENESIS
MUTAGENS
NUCLEIC ACID REPLICATION
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
RADIATION EFFECTS
RADIATIONS
RATS
RODENTS
SOMATIC CELLS
SULFONIC ACID ESTERS
TRITIUM COMPOUNDS
ULTRAVIOLET RADIATION
VERTEBRATES
VITAMIN A
VITAMINS