Lack of covalent binding to DNA of di-n-octyltin dichloride (DOTC) in vivo and in vitro.
[14C]Di-n-octyltin dichloride ([14C]DOTC) was administered by oral gavage to male and female rats. After 96 h hepatic and thymic DNA was isolated. All DNA fractions were radioactive, but analysis of DNA hydrolysates by HPLC revealed that the radioactivity was incorporated via biosynthesis and was not due to adduct formation. The limit of detection for adduct formation, expressed in units of the covalent binding index (CBI = mumol chemical bound per mol nucleotides/mmol chemical applied per kg body wt.) was approximately 0.2 for liver DNA and about 0.7 for thymus DNA. This maximum possible DNA-binding ability is about 30,000 times lower than the corresponding value for the strong carcinogen, aflatoxin B1. In addition, [14C]DOTC did not bind covalently to calf thymus DNA in the presence or absence of rat liver S9 or to DNA of V79 Chinese hamster cells. This study therefore gives no indication for genotoxic activity of DOTC mediated by DNA binding.
Sagelsdorff
P
P
Central Toxicology Unit, CIBA-GEIGY Ltd., Basel, Switzerland.
Dollenmeier
P
P
Ebner
D
D
Bieri
F
F
Kelly
S M
SM
Stäubli
W
W
Waechter
F
F
Bentley
P
P
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002417:Cattle; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage; D005260:Female; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D009153:Mutagens / Q000378:metabolism; D009947:Organotin Compounds / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013950:Thymus Gland / Q000378:metabolism
D009153:Mutagens; D009947:Organotin Compounds; D004247:DNA; C020297:di-n-octyltin dichloride