Inhibition of benzo[a]pyrene-7,8-diol formation in vitro by complex organic mixtures.
Coal-derived complex organic mixtures [COM] with boiling points greater than or equal to 370 degrees C (greater than or equal to 700 degrees F) are known to inhibit both mouse skin tumor initiation by benzo[a]pyrene [BAP], and BAP-induced bacterial mutagenesis. We have examined the effects of 5 COM, with boiling points of 149-370 degrees C (300-700 degrees F), 370-398 degrees C (700-750 degrees F), 398-426 degrees C (750-800 degrees F), 426-454 degrees C (800-850 degrees F), and greater than 454 degrees C (greater than 850 degrees F), on both the rate and the route of BAP metabolism by rat liver homogenates in vitro. When co-metabolized in 40:1 excess with BAP, all of the COM reduced the rate of BAP metabolism. The 149-370 degrees C (300-700 degrees F) COM reduced the initial rate of BAP metabolism to 34% of the rate for BAP alone, while the four higher-boiling COM reduced it to 6.3-9.3% of the rate for BAP alone. In addition, the 2 highest-boiling COM (426-454 degrees C and greater than 454 degrees C boiling points) were found to reduce the percentage of BAP metabolized to BAP-7,8-diol, in comparison to incubations using BAP alone. The 370-398 degrees C and 398-426 degrees C COM did not alter the percentage of BAP metabolized to BAP-7,8-diol, while the 149-370 degrees C COM increased it. Both the general inhibition of BAP metabolism (by all of the COM), and the specific inhibition of BAP-7,8-diol formation (by the highest-boiling COM) may play a role in the inhibition of formation of BAP-induced skin tumors by these materials.
Dankovic
D A
DA
Northwest College and University Association, Richland, WA 99352.
Thomas
B L
BL
Zangar
R C
RC
Later
D W
DW
Springer
D L
DL
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001711:Biotransformation / Q000187:drug effects; D004101:Dihydroxydihydrobenzopyrenes / Q000096:biosynthesis*; D006838:Hydrocarbons / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012997:Solvents / Q000494:pharmacology*; D013997:Time Factors
D001140:Aroclors; D004101:Dihydroxydihydrobenzopyrenes; D006838:Hydrocarbons; D012997:Solvents; C017228:benzo(a)pyrene 7,8-dihydrodiol; D001564:Benzo(a)pyrene