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
✍ Scribed by John D. Budroe; Joseph G. Shaddock; Daniel A. Casciano
- Publisher
- John Wiley and Sons
- Year
- 1987
- Tongue
- English
- Weight
- 625 KB
- Volume
- 10
- Category
- Article
- ISSN
- 0893-6692
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✦ Synopsis
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 pM to 50 pM. Retinol and retinoic acid did not significantly affect 200 pg/mL ethyl methanesulfonate(EMS)-or 32 J/m2 ultraviolet light(UV)-induced UDS at concentrations ranging from 1 pM to 50 pM. In contrast, retinol and retinoic acid significantly inhibited 2.5 pg/mL and 5.0 pg/mL 7,12-dimethyl-benz[a]anthracene(DMBA)-induced UDS at concentrations of 1 pM or greater. Retinoland 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 pM and 100 pM. 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.