LaVoie E J, He Z M, Meegalla R L, Weyand E H
Rutgers University, College of Pharmacy, Piscataway, NJ 08855-0789.
Cancer Lett. 1993 Jun 15;70(1-2):7-14. doi: 10.1016/0304-3835(93)90068-k.
Exceptional tumorigenic potency was observed with 4-fluorobenzo[j]fuoranthene (4-fluoroB[j]F) relative to benzo[j]fluoranthene (B[j]F) and 10-fluorobenzo[j]fluoranthene (10-fluoroB[j]F) in a mouse skin initiation promotion bioassay. Comparison of the tumorigenic response obtained at total initiating doses of 50, 100, and 1000 nmol firmly established the greater tumorigenic potency of 4-fluoroB[j]F. B[j]F produced a significant tumorigenic response only at total initiating doses of 100 and 1000 nmol per mouse. 10-FluoroB[j]F produced a significant tumorigenic response only at the highest initiating dose, 1000 nmol per mouse. In contrast, 4-fluoroB[j]F produced a significant tumorigenic response at all three doses. At a total initiating dose of 50 nmol, a 90% incidence of tumor-bearing mice with an average of 3.05 tumors per mouse was observed with 4-fluoroB[j]F. A second initiation promotion bioassay was performed to establish the tumorigenic potency of 4-fluoroB[j]F relative to benzo[a]-pyrene (B[a]P), 7,12-dimethylbenz[a]anthracene (DMBA), and dibenzo[a,l]pyrene (DB[a,l]P). 4-FluoroB[j]F did exhibit significant tumor-initiating activity at doses of 10 and 25 nmol per mouse, inducing a 45 and 60% incidence of tumor-bearing mice with an average of 0.75 and 1.65 tumors per mouse, respectively. While B[a]P was not tumorigenic at these doses, DMBA and DB[a,l]P exhibited significant tumorigenic activity at doses of 1, 4, 10, and 25 nmol per mouse. DB[a,l]P induced a 95% incidence of tumor-bearing mice with an average of 5.0 tumors per mouse at a total initiator dose of 1 nmol. DMBA at this dose produced an 85% incidence of tumor-bearing mice with an average of 1.30 tumors per mouse. The results of these initiation promotion bioassays clearly demonstrate that 4-fluoroB[j]F is significantly more active than B[j]F, 10-fluoroB[j]F and B[a]P and less active than either DMBA or DB[a,l]P as a tumor initiator on mouse skin.
在小鼠皮肤启动促进生物测定中，相对于苯并[j]荧蒽（B[j]F）和10-氟苯并[j]荧蒽（10-氟B[j]F），观察到4-氟苯并[j]荧蒽（4-氟B[j]F）具有异常高的致瘤潜能。在总启动剂量为50、100和1000 nmol时获得的致瘤反应比较，有力地证实了4-氟B[j]F具有更强的致瘤潜能。仅在每只小鼠总启动剂量为100和1000 nmol时，B[j]F才产生显著的致瘤反应。10-氟B[j]F仅在最高启动剂量（每只小鼠1000 nmol）时产生显著的致瘤反应。相比之下，4-氟B[j]F在所有三个剂量下均产生显著的致瘤反应。在总启动剂量为50 nmol时，用4-氟B[j]F观察到90%的荷瘤小鼠发生率，平均每只小鼠有3.05个肿瘤。进行了第二次启动促进生物测定，以确定4-氟B[j]F相对于苯并[a]芘（B[a]P）、7,12-二甲基苯并[a]蒽（DMBA）和二苯并[a,l]芘（DB[a,l]P）的致瘤潜能。4-氟B[j]F在每只小鼠剂量为10和25 nmol时确实表现出显著的肿瘤启动活性，分别诱导45%和60%的荷瘤小鼠发生率，平均每只小鼠有0.75和1.65个肿瘤。虽然B[a]P在这些剂量下不具有致瘤性，但DMBA和DB[a,l]P在每只小鼠剂量为1、4、10和25 nmol时表现出显著的致瘤活性。在总启动剂量为1 nmol时，DB[a,l]P诱导95%的荷瘤小鼠发生率，平均每只小鼠有5.0个肿瘤。在此剂量下，DMBA产生85%的荷瘤小鼠发生率，平均每只小鼠有1.30个肿瘤。这些启动促进生物测定的结果清楚地表明，作为小鼠皮肤的肿瘤启动剂，4-氟B[j]F比B[j]F、10-氟B[j]F和B[a]P活性显著更高，而比DMBA或DB[a,l]P活性更低。
