Vitamin E protects against methyl ethyl ketone peroxide-induced peroxidative damage to rat brain DNA.
Peroxidative damage to DNA initiated by methyl ethyl ketone peroxide, a potent initiator of lipid peroxidation, and protection against this damage by vitamin E were studied in rats. Groups of rats were fed a casein-based diet that contained 10% tocopherol-stripped corn oil and either 0, 3, 5, or 10 IU of DL-alpha-tocopherol acetate/kg; the groups were named 0, 3, 5, or 10, respectively. DNA isolated from the brains of these rats was analyzed for template activity, bound tryptophan, and malondialdehyde-type DNA-protein and interstrand DNA crosslinks. The DNA of groups 5 and 10 had significantly higher template activity, less bound tryptophan, and fewer crosslinks than that of groups 3 and 5, respectively. The DNA of group 3 had significantly fewer interstrand DNA crosslinks than that of group 0, and the most significant differences were between groups 3 and 5. Loss of template activity correlated best with interstrand DNA crosslinks, and bound tryptophan correlated best with DNA-protein crosslinks. Electrophoresis of the RNA transcribed from the isolated DNA showed that a significantly higher percentage of longer RNA was made from the DNA of groups 5 and 10 than from that of group 0. The apparent molecular weight of the DNA of group 0 was less than that of group 10 and was more heterogeneous, which suggests fragmentation and/or crosslinking. The DNA from group 10 had maximum observed template activity; therefore, 10 IU of vitamin E/kg of diet appeared to be adequate to protect brain DNA against the damage measured in this study.
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002074:Butanones / Q000037:antagonists & inhibitors*; D004247:DNA / Q000235:genetics; D008297:Male; D008970:Molecular Weight; D009154:Mutation / Q000187:drug effects*; D010545:Peroxides / Q000037:antagonists & inhibitors*; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D014158:Transcription, Genetic; D014364:Tryptophan / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
D002074:Butanones; D010545:Peroxides; C011007:methyl ethyl ketone peroxide; D014810:Vitamin E; D012313:RNA; D014364:Tryptophan; D004247:DNA