DNA damage, repair, and replication in selenite-induced cataract in rat lens.
DNA synthesis was evaluated in vitro by measuring incorporation of 3H-thymidine in rat lens following systemic delivery of a cataractogenic dose of selenite. Among early metabolic changes observed in the lenses of rats receiving a single dose of 30 nmol Na2SeO3/g body weight was a 30% decrease in DNA replication in lens epithelium occurring between 6 and 12 h after administration of the selenite. This change was followed by an 80% increase in replication by 24 h. Thymidine incorporation in DNA remained elevated compared to controls through 96 h. Unscheduled DNA synthesis was found to be approximately 10% of the total DNA formed, but there was a 30% and 70% increase of this putative DNA repair in the lenses from selenite-treated animals at 6 and 24 h after the injection. Using the alkaline unwinding assay, the proportion of single-strand DNA in lenses from selenite-treated animals increased after 24 h. This estimate of DNA damage was greater in lenses after 96 h. Each component of DNA metabolism: damage, repair, and replication, was affected by the occurrence of selenite stress in lens. These changes both preceded and accompanied nuclear cataract formation.
Huang
L L
LL
Department of Biochemistry and Nutrition, Virginia Polytechnic Institute and State University, Blacksburg 24061-0308.
Hess
J L
JL
Bunce
G E
GE
D000818:Animals; D002386:Cataract / Q000139:chemically induced*; D002845:Chromatography; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication / Q000187:drug effects; D006918:Hydroxyurea / Q000494:pharmacology; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000633:toxicity*; D018036:Selenium Compounds; D064588:Selenium Oxides; D013936:Thymidine / Q000378:metabolism
D018036:Selenium Compounds; D064588:Selenium Oxides; D004247:DNA; D012643:Selenium; D013936:Thymidine; D006918:Hydroxyurea