Weyand E H, Geddie N, Rice J E, Czech A, Amin S, LaVoie E J
American Health Foundation, Naylor Dana Institute for Disease Prevention, Valhalla, NY 10595.
Carcinogenesis. 1988 Jul;9(7):1277-81. doi: 10.1093/carcin/9.7.1277.
The metabolism of 3-, 8- and 9-fluorobenzo[k]fluoranthene (B[k]F) relative to B[k]F was investigated. The major metabolites of B[k]F formed in vitro using rat liver S-9 metabolism systems were 8,9-dihydro-8,9-dihydroxyB[k]F, the 2,3-quinone of B[k]F and 3-, 8- and 9-hydroxyB[k]F. Fluorine substitution within the structure of B[k]F substantially altered the types of metabolites formed in vitro. The most pronounced effect was observed with 9-fluoroB[k]F. In contrast to B[k]F, the 8,9-dihydro-8,9-dihydroxy-, 9-hydroxy- and 10,11-dihydro-10,11-dihydroxy derivatives were not detected as metabolites of 9-fluoroB[k]F. However, either the 2,3- or 4,5-dihydrodiol of 9-fluoroB[k]F was detected. In the case of 8-fluoroB[k]F, neither the 8- nor 11-hydroxy- derivatives were detected. The principle dihydrodiols formed from 8-fluoroB[k]F were the 10,11-dihydrodiol and either the 2,3-or 4,5-dihydrodiol. The pattern of metabolites formed with 3-fluoroB[k]F was similar to that observed with B[k]F with the exception that neither the 3- nor 4-hydroxy derivatives were formed. Mass spectral data indicated that fluoro substitution is not lost to any appreciable extent during the metabolism of 3-, 8- and 9-fluoroB[k]F. The mutagenic activity of these B[k]F fluoro derivatives along with B[k]F, 2,3-dihydro-2,3-dihydroxyB[k]F, the 2,3-quinone of B[k]F and 8,9-dihydro-8,9-dihydroxyB[k]F were evaluated in Salmonella typhimurium TA100 in the presence of rat liver S-9 metabolism systems. 3-FluoroB[k]F was more mutagenic than B[k]F, while both 8- and 9-fluoroB[k]F were less active. While the 2,3-dihydrodiol and 2,3-quinone were weakly active, the 8,9-dihydrodiol had similar mutagenic potency to B[k]F.
研究了3-、8-和9-氟苯并[k]荧蒽（B[k]F）相对于B[k]F的代谢情况。使用大鼠肝脏S-9代谢系统在体外形成的B[k]F的主要代谢产物为8,9-二氢-8,9-二羟基B[k]F、B[k]F的2,3-醌以及3-、8-和9-羟基B[k]F。B[k]F结构中的氟取代显著改变了体外形成的代谢产物类型。9-氟B[k]F的影响最为明显。与B[k]F不同，未检测到8,9-二氢-8,9-二羟基-、9-羟基-和10,11-二氢-10,11-二羟基衍生物作为9-氟B[k]F的代谢产物。然而，检测到了9-氟B[k]F的2,3-或4,5-二氢二醇。对于8-氟B[k]F，未检测到8-或11-羟基衍生物。由8-氟B[k]F形成的主要二氢二醇是10,11-二氢二醇以及2,3-或4,5-二氢二醇。3-氟B[k]F形成的代谢产物模式与B[k]F相似，只是未形成3-或4-羟基衍生物。质谱数据表明，在3-、8-和9-氟B[k]F的代谢过程中，氟取代不会有明显损失。在大鼠肝脏S-9代谢系统存在的情况下，在鼠伤寒沙门氏菌TA100中评估了这些B[k]F氟衍生物以及B[k]F、2,3-二氢-2,3-二羟基B[k]F、B[k]F的2,3-醌和8,9-二氢-8,9-二羟基B[k]F的诱变活性。3-氟B[k]F比B[k]F更具诱变活性，而8-和9-氟B[k]F的活性均较低。虽然2,3-二氢二醇和2,3-醌的活性较弱，但8,9-二氢二醇的诱变效力与B[k]F相似。
