LaVoie E J, He Z M, Wu Y, Meschter C L, Weyand E H
Rutgers, State University of New Jersey, College of Pharmacy, Department of Pharmaceutical Chemistry, Piscataway 08855-0789.
Cancer Res. 1994 Feb 15;54(4):962-8.
Benzo[j]fluoranthene (B[j]F), trans-4,5-dihydro-4,5-dihydroxy-B[j]F, and trans-9,10-dihydro-9,10-dihydroxy-B[j]F were evaluated for tumorigenic activity in newborn CD1 mice. These dihydrodiols were assayed at doses of 1.10 and 0.275 mumol/mouse. B[j]F and the syn- and anti-diol epoxides derived from these dihydrodiols were evaluated at doses of 1.10, 0.275, and 0.110 mumol/mouse (80 mice/group). trans-4,5-Dihydro-4,5-dihydroxy-B[j]F was more potent than trans-9,10-dihydro-9,10-dihydroxy-B-[j]F in inducing pulmonary tumors in both female and male mice. Administration of 1.10 mumol of trans-4,5-dihydro-4,5-dihydroxy-B[j]F resulted in a 90-92% incidence of pulmonary tumors with an average of 3.6 and 4.2 tumors/mouse among female and male mice, respectively. A similar tumorigenic activity was observed for B[j]F in lung. trans-9,10-Dihydro-9,10-dihydroxy-B[j]F was significantly less tumorigenic (P < 0.05), producing a 44 and 64% incidence of pulmonary tumors at a dose of 1.10 mumol with an average of 0.8 and 1.0 tumor/mouse in female and male mice, respectively. A statistically significant (P < 0.001) incidence of hepatic tumors was also produced among male mice administered either B[j]F, trans-4,5-dihydro-4,5-dihydroxy-B[j]F, or trans-9,10-dihydro-9,10-dihydroxy-B[j]F at a dose of 1.10 mumol/mouse. In comparing the tumorigenicity of the diasteromeric diol epoxides derived from both trans-4,5-dihydro-4,5-dihydroxy-B[j]F and trans-9,10-dihydro-9,10-dihydroxy-B[j]F, the anti-diasteromers exhibited greater tumorigenic activity. The most tumorigenic diol epoxide was anti-4,5-dihydroxy-6,6a-epoxy-4,5,6,6a-tetrahydro-B[j]F. At a dose of 0.275 mumol, this diol epoxide induced a 96 and 100% incidence of pulmonary tumors in female and male mice, with an average of 8.6 and 5.0 tumors/mouse, respectively. anti-9,10-Dihydroxy-11,12-epoxy-9,10,11,12-tetrahydro-B[j]F at this dose produced a 56 and 95% incidence of pulmonary tumors in female and male mice with an average of 1.0 and 2.8 tumors/mouse, respectively. syn-4,5-Dihydroxy-6,6a-epoxy-4,5,6,6a-tetrahydro-B[j]F and syn-9,10-dihydroxy-11,12-epoxy-9,10,11,12-tetrahydro-B[j]F at a dose of 0.275 mumol did not induce a significant incidence (P > 0.05) of pulmonary tumors in female or male mice.(ABSTRACT TRUNCATED AT 400 WORDS)
对苯并[j]荧蒽（B[j]F）、反式-4,5-二氢-4,5-二羟基-B[j]F和顺式-9,10-二氢-9,10-二羟基-B[j]F进行了新生CD1小鼠的致癌活性评估。这些二氢二醇以1.10和0.275 μmol/小鼠的剂量进行测定。B[j]F以及由这些二氢二醇衍生的顺式和反式二醇环氧化物以1.10、0.275和0.110 μmol/小鼠的剂量进行评估（每组80只小鼠）。反式-4,5-二氢-4,5-二羟基-B[j]F在雌性和雄性小鼠中诱导肺部肿瘤方面比反式-9,10-二氢-9,10-二羟基-B[j]F更具效力。给予1.10 μmol的反式-4,5-二氢-4,5-二羟基-B[j]F，雌性和雄性小鼠肺部肿瘤的发生率分别为90 - 92%，平均每只小鼠有3.6个和4.2个肿瘤。在肺部观察到B[j]F有类似的致癌活性。反式-9,10-二氢-9,10-二羟基-B[j]F的致癌性明显较低（P < 0.05），在1.10 μmol的剂量下，雌性和雄性小鼠肺部肿瘤的发生率分别为44%和64%，平均每只小鼠有0.8个和1.0个肿瘤。在以1.10 μmol/小鼠的剂量给予B[j]F、反式-4,5-二氢-4,5-二羟基-B[j]F或反式-9,10-二氢-9,10-二羟基-B[j]F的雄性小鼠中，也产生了具有统计学意义（P < 0.001）的肝脏肿瘤发生率。在比较由反式-4,5-二氢-4,5-二羟基-B[j]F和反式-9,10-二氢-9,10-二羟基-B[j]F衍生的非对映二醇环氧化物的致癌性时，反式非对映体表现出更大的致癌活性。最具致癌性的二醇环氧化物是反式-4,5-二羟基-6,6a-环氧-4,5,6,6a-四氢-B[j]F。在0.275 μmol的剂量下，这种二醇环氧化物在雌性和雄性小鼠中诱导肺部肿瘤的发生率分别为96%和100%，平均每只小鼠分别有8.6个和5.0个肿瘤。在该剂量下，反式-9,10-二羟基-11,12-环氧-9,10,11,12-四氢-B[j]F在雌性和雄性小鼠中诱导肺部肿瘤的发生率分别为56%和95%，平均每只小鼠分别有1.0个和2.8个肿瘤。在0.275 μmol的剂量下，顺式-4,5-二羟基-6,6a-环氧-4,5,6,6a-四氢-B[j]F和顺式-9,10-二羟基-11,12-环氧-9,10,11,12-四氢-B[j]F在雌性或雄性小鼠中未诱导出显著的肺部肿瘤发生率（P > 0.05）。（摘要截断于400字）
