DNA adducts in rat lung, liver and peripheral blood lymphocytes produced by i.p. administration of benzo[a]pyrene metabolites and derivatives.
DNA adducts produced in vivo in rat lung, liver and peripheral blood lymphocytes following the i.p. administration of several synthetic benzo[a]pyrene (B[a]P) metabolites and ring-substituted derivatives have been analyzed by the nuclease P1 version of the 32P-postlabeling assay. These include 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11- and 12-hydroxy-B[a]P, (+/-)-B[a]P-trans-4,5-dihydrodiol, (+/-)-B[a]P-trans-7,8-dihydrodiol, (+/-)-B[a]P-trans-9,10-dihydrodiol and B[a]P-7,8-dione. Among the monohydroxy derivatives, only 2-, 9- and 12-hydroxy-B[a]P produced detectable adducts. The only disubstituted derivative studied that produced adducts was the trans-7,8-dihydrodiol. The resulting DNA adducts were compared to those produced in each tissue by administration of B[a]P. 9-Hydroxy-B[a]P and B[a]P-trans-7,8-dihydrodiol each lead to the formation of major B[a]P adducts seen in lung and liver respectively. None of the adducts derived from either 2-hydroxy-B[a]P or 12-hydroxy-B[a]P were observed following administration of B[a]P alone.
Ross
J
J
Carcinogenesis and Metabolism Branch, US Environmental Protection Agency, Research Triangle Park, NC 27711.
Nelson
G
G
Erexson
G
G
Kligerman
A
A
Earley
K
K
Gupta
R C
RC
Nesnow
S
S
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism; D000818:Animals; D001564:Benzo(a)pyrene / Q000031:analogs & derivatives / Q000378:metabolism*; D001580:Benzopyrenes / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts; D004101:Dihydroxydihydrobenzopyrenes / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001580:Benzopyrenes; D018736:DNA Adducts; D004101:Dihydroxydihydrobenzopyrenes; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; C023394:2-hydroxybenzo(a)pyrene; D004247:DNA