Arsenic inhibits the repair of DNA damage induced by benzo(a)pyrene.
In order to study the effect of arsenic on DNA damage, Sprague-Dawley rats were dosed with sodium arsenite (10 mg/kg) with or without 800 microg of benzo(a)pyrene (BP) by intramammilary injection. The animals were sacrificed on day 1, 3, 5, 10 and 27 and the mammary gland tissues were collected for DNA adduct measurement using a (32)P post-labeling assay. Animals dosed with arsenic alone did not show any DNA adducts. DNA adduct levels in rats dosed with BP alone reached a maximum level by day 5, reducing to 13% of this level by day 27. Adduct levels in rats dosed with arsenic and BP also reached a maximum by day 5 but only 80% of the level observed in the BP group. However, 84% of this amount still remained by day 27. The First Nucleotide Change (FNC) technique was used for the screening of 115 samples of various tissues from mice that had been chronically exposed to sodium arsenate for over 2 years revealed that inorganic arsenic did not attack the two putative hotspots (codons 131 and 154) of the hOGG1 gene. These results support the hypothesis that arsenic exerts its biological activity through DNA repair inhibition.
Tran
Huu-Phuc
HP
National Research Centre for Environmental Toxicology, 39 Kessels Road, Coopers Plains, Brisbane, Qld 4108 Australia.
Prakash
Arungundrum S
AS
Barnard
Ross
R
Chiswell
Barry
B
Ng
Jack C
JC
D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001940:Breast / Q000187:drug effects; D018736:DNA Adducts / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005260:Female; D051379:Mice; D016296:Mutagenesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017670:Sodium Compounds / Q000633:toxicity*
D018053:Arsenites; D018736:DNA Adducts; D004791:Enzyme Inhibitors; D017670:Sodium Compounds; D001564:Benzo(a)pyrene; C017947:sodium arsenite