Formation and persistence of ethylguanines in liver DNA of rainbow trout (Salmo gairdneri) treated with diethylnitrosamine by water exposure.
Diethylnitrosamine exposure via the water resulted in the formation of 7-ethylguanine and O6-ethylguanine in rainbow trout liver DNA. The modified bases were quantitated by high-pressure liquid chromatography and fluorescence spectrophotometry. In vivo 7-ethylguanine and O6-ethylguanine levels were directly proportional to DEN concentrations between 62.5 and 250 ppm. 7-Ethylguanine and O6-ethylguanine levels were approximately directly proportional to duration of exposure to DEN between 0 and 6 hr under the conditions used, with less than proportionate increases thereafter. Removal of ethylguanines from liver DNA following a 24-hr exposure to 250 ppm DEN (a known carcinogenic regimen) was biphasic; 24% of the O6-ethylguanine and 32% of the 7-ethylguanine found immediately after exposure were removed in 12 hr but no significant decline was found over the period from 12 to 96 hr after exposure. Alkyl acceptor protein activity in trout liver was examined to assess the role of enzymatic repair in the observed loss of O6-ethylguanine in vivo. Although an O6-alkylguanine repair system similar to the alkyltransferase system reported in rodents was found in trout liver, only 4% of the O6-ethylguanine lost from DNA after exposure to 250 ppm DEN can be accounted for by activity of the alkyl acceptor protein. The high incidence of liver tumours observed in DEN-treated rainbow trout may be related to the rapid formation and substantial persistence of the promutagenic O6-ethylguanine in liver DNA.
Fong
A T
AT
Department of Food Science and Technology, Oregon State University, Corvallis 97331.
Hendricks
J D
JD
Dashwood
R H
RH
Van Winkle
S
S
Bailey
G S
GS
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004052:Diethylnitrosamine / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D014337:Trout; D014867:Water
D014867:Water; C022007:7-ethylguanine; D004052:Diethylnitrosamine; C007673:6-ethylguanine; D006147:Guanine; D004247:DNA