DNA adduct formation by secondary metabolites of cyclopenta[cd]pyrene in vitro.
In this study, calf thymus DNA was reacted in vitro with cyclopenta[cd]pyrene 3,4-epoxide (CPPE) or its metabolites, 3,4-dihydroCPP-3,4-diol (CPP-3,4-diol) and 4-hydroxy-3,4-dihydroCPP (4-OH-DCPP), activated with sulfotransferase. The adducts formed were analyzed by HPLC with fluorescence detection following enzymatic digestion of DNA to deoxynucleosides. We have shown previously that the major CPPE-reacted DNA adducts are cis-3-(deoxyguanosin-N2-yl)-4-hydroxy-3,4-dihydroCPP. Sulfotransferase activation of trans-CPP-3,4-diol yielded two adducts that were identical to the products resulting from the reaction of CPPE with DNA, while cis-CPP-3,4-diol gave very low covalent binding. Two adducts formed by sulfotransferase activation of 4-OH-DCPP were identical to the products of the reaction of synthetic 4-NaO3S-O-DCPP or sulfotransferase-activated 4-OH-DCPP with deoxyguanosine. These results indicate that guanine is the predominant site of CPP adduct formation in DNA, and that the 4-hydroxy-3-dGuo adducts can arise by reaction of DNA with either CPPE or sulfotransferase-activated trans-CPP-3,4-diol.
Hsu
C H
CH
Division of Bioengineering and Environmental Health, Massachusetts Institute of Technology, Cambridge 02139, USA.
Skipper
P L
PL
Tannenbaum
S R
SR
D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism*; D006147:Guanine / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism*; D011721:Pyrenes / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism
D018736:DNA Adducts; D009153:Mutagens; D011721:Pyrenes; D006147:Guanine; D004247:DNA; D015238:Sulfotransferases; C027599:cyclopenta(cd)pyrene 3,4-oxide