Investigations on the relationship between DNA ethenobase adduct levels in several organs of vinyl chloride-exposed rats and cancer susceptibility.
The levels of 1,N6-ethenodeoxyadenosine (epsilon dAdo) and 3,N4-ethenodeoxycytidine (epsilon dCyd) were measured in DNA of several target organs of vinyl chloride (VC)-exposed rats. Seven-day-old (group I) and 13-week-old (group II) BD VI rats were exposed during 2 weeks to 500 ppm VC in air (7 hr per day and 7 days per week). epsilon dAdo and epsilon dCyd were measured by a combination of prepurification of DNA hydrolysates by HPLC and competitive radioimmunoassay using specific murine monoclonal antibodies. Both ethenodeoxynucleosides were detected in liver, lungs and brain (levels ranging from 0.6 x 10(-7) to 1.3 x 10(-7) for epsilon dAdo/2'-deoxyadenosine and from 1.95 x 10(-7) to 4.92 x 10(-7) for epsilon dCyd/2'-deoxycytidine) but not in kidneys of group I rats. In group II rats, only liver DNA was analysed and the levels of each adduct were six times lower than in young (group II) rats. These findings are in good agreement with the organotropism and the age-related sensitivity of VC-induced carcinogenesis in rodents.
Ciroussel
F
F
Unit of Environmental Carcinogens & Host Factors, Lyon, France.
Barbin
A
A
Eberle
G
G
Bartsch
H
H
D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D003839:Deoxyadenosines / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000378:metabolism; D004198:Disease Susceptibility; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D014752:Vinyl Chloride / Q000633:toxicity*; D014753:Vinyl Compounds / Q000633:toxicity*
D003839:Deoxyadenosines; D014753:Vinyl Compounds; D003841:Deoxycytidine; C032221:1,N(6)-ethenodeoxyadenosine; C032222:3,N(4)-ethenodeoxycytidine; D004247:DNA; D014752:Vinyl Chloride