ABSTRACT
Administration of hepatocarcinogens aflatoxin B1 and N-nitrosodimethylamine to rats caused single-strand breaks in nuclear DNA. Inclusion in the diet of rutin, a naturally occurring phenolic flavonoid glycoside, significantly reduced the appearance of such breaks. The protection against DNA damage was found to be reduction in the induction of repair enzymes polymerase, DNA polymerase beta and DNA ligase. Even associated with poly(ADP-ribose) a marginal dose of rutin was effective in this regard. Since DNA damage and inefficient repair are expected to initiate the process of carcinogenesis, modulation by rutin of these parameters emphasizes the protective role of this flavonoid against carcinogenesis induced by chemical carcinogens.
Subject(s)
DNA Damage/drug effects , DNA Ligases/metabolism , DNA/drug effects , Rutin/pharmacology , Aflatoxin B1/toxicity , Animals , Carcinogens/toxicity , Dimethylnitrosamine/toxicity , Enzyme Induction/drug effects , Male , Rats , Rats, WistarABSTRACT
The activity of some nuclear enzymes associated with DNA repair was examined following aflatoxin B1 administration in rats maintained on different levels of dietary copper. Induction of poly(ADP-ribose) polymerase, DNA polymerase beta and DNA ligase was found to be significantly higher in copper-deficient rats. Copper supplementation, even at marginal doses, was able to bring down the induction to the level observed in normal rats. The results emphasize the protective role of copper against the DNA damaging effects of aflatoxin B1.
Subject(s)
Aflatoxin B1/pharmacology , Copper/pharmacology , DNA Repair/drug effects , Enzymes/drug effects , Mutagens/pharmacology , Animals , Copper/deficiency , DNA Ligases/drug effects , DNA Ligases/metabolism , DNA Polymerase I/drug effects , DNA Polymerase I/metabolism , Diet , Enzymes/metabolism , Male , Poly(ADP-ribose) Polymerases/drug effects , Poly(ADP-ribose) Polymerases/metabolism , Rats , Rats, Wistar , WeaningABSTRACT
Formation of single strand breaks in nuclear DNA induced by hepatocarcinogens aflatoxin B1 and N-nitrosodimethylamine was observed to be more pronounced in rats maintained on a riboflavin-deficient diet compared to that on a normal diet. This increased damage was reversed on riboflavin supplementation. The induction of repair enzymes poly(ADP-ribose) polymerase, DNA polymerase beta and DNA ligase was significantly higher in riboflavin-deficient rats following DNA damage caused by the administration of carcinogens. Riboflavin supplementation brought down the induction to the levels found in rats maintained on normal diet. Since damage to DNA and its altered repair may relate to carcinogenesis, modulation of these parameters by riboflavin suggests a potential chemopreventive role of this vitamin.
Subject(s)
Carcinogens/toxicity , DNA Damage , DNA Ligases/metabolism , Riboflavin/pharmacology , Aflatoxin B1/pharmacology , Animals , DNA Ligases/biosynthesis , DNA Ligases/drug effects , DNA, Single-Stranded/drug effects , DNA, Single-Stranded/metabolism , Enzyme Induction/drug effects , Male , Rats , Rats, Wistar , Riboflavin Deficiency/enzymologyABSTRACT
The effect of different vitamin A status on events following DNA damage by hepatocarcinogens was investigated in rats. Formation of single-strand breaks in nuclear DNA induced by aflatoxin B1 and N-nitrosodimethylamine was observed to be more pronounced after vitamin A-deficiency. This enhanced damage was reversed upon vitamin A supplementation. Subsequent to DNA damage, the induction of repair enzymes poly(ADP-ribose) polymerase, DNA polymerase beta and DNA ligase was found to be significantly higher in vitamin A-deficient rats. Vitamin A supplementation brought down the induction to the levels found in rats maintained on normal diet. Vitamin A thus may control carcinogenesis by manipulating molecular events at the initiation stage.
