Tumorigenicity of nitrated derivatives of pyrene, benz[a]anthracene, chrysene and benzo[a]pyrene in the newborn mouse assay.
Tumorigenicity of nitrated derivatives of pyrene, benz[a]anthracene, chrysene and benzo[a]pyrene in the newborn mouse assay.
复制标题
芘、苯并[a]蒽、屈和苯并[a]芘的硝化衍生物在新生小鼠试验中的致瘤性。
作者：
P. Wislocki;E. Bagan;A. Y. Lu;K. Dooley;P. Fu;H. Han;F. Beland;F. Kadlubar
本文报道了8种硝基多环芳烃（PAHs），包括1-和4-硝基芘、1，3-、1，6-和1，8-二硝基芘、7-硝基苯并[a]蒽、6-硝基蒽和6-硝基苯并[a]芘及其母体化合物，在生后1、8和15天腹腔注射给药，在小鼠体内的致瘤性。芘和1-硝基芘在雄性小鼠中诱导的肝肿瘤发生率相似，在每只小鼠总剂量为700和2800 nmol时，肿瘤发生率分别为12-15%和21-28%。雌性动物中未发生肝肿瘤，两种性别动物中3-10%的肺肿瘤产率与溶剂处理对照组中的结果相似。假定的近似致癌物，1-亚硝基芘，在700 nmol每只小鼠，导致肝脏肿瘤的45%的男性和9%的女性。4-硝基芘比芘或1-硝基芘更具致瘤性;在2800 nmol的剂量下，它在83%的男性和7%的女性中诱导肝脏肿瘤，肺肿瘤产量分别为38%和31%。用200 nmol的1，3-、1，6-或1，8-二硝基芘处理的雌性小鼠没有发生肝肿瘤，但雄性小鼠的肝肿瘤发生率分别为20%、32%和16%，显著高于用芘处理的小鼠。在给予2800 nmol苯并[a]蒽的雄性小鼠中，肝肿瘤发生率为79%，而7-硝基苯并[a]蒽治疗的发生率仅为28%。同样，560 nmol苯并[a]芘会导致男性肝脏肿瘤发生率为49%，而给予6-硝基苯并[a]芘的男性肝脏肿瘤发生率为28%。苯并[a]芘处理还诱导雄性和雌性小鼠的肺肿瘤发生率分别为35%和48%，而6-硝基苯并[a]芘处理小鼠的相应值分别为14%和2%。以2800 nmol/只小鼠给药的克雷伯胺分别在41%和21%的雄性动物中诱导了肝肿瘤和肺肿瘤;在700 nmol剂量下，仅在29%的雄性动物中诱导了肝肿瘤，而在雌性动物中没有诱导肝肿瘤。相比之下，以每只小鼠700 nmol的6-硝基金黄色葡萄球菌给药，雄性和雌性小鼠的肝肿瘤发生率分别为76%和23%。（400字处截断摘要）
Eight nitropolycyclic aromatic hydrocarbons (PAHs), including 1- and 4-nitropyrene, 1,3-, 1,6- and 1,8-dinitropyrene, 7-nitrobenz[a]anthracene, 6-nitrochrysene and 6-nitrobenzo-[a]pyrene and their parent PAHs were tested fro tumorigenicity in the newborn mouse model by i.p. administration at 1, 8, and 15 days after birth. Both pyrene and 1-nitropyrene induced similar incidences of hepatic tumors in males, yielding a 12-15% and a 21-28% tumor incidence at total doses of 700 and 2800 nmol per mouse, respectively. Liver tumors did not occur in females and the 3-10% lung tumor yield in both sexes was similar to that found in solvent-treated controls. The presumed proximate carcinogen, 1-nitrosopyrene, administered at 700 nmol per mouse, caused liver tumors in 45% of the males and in 9% of the females. 4-Nitropyrene was more tumorigenic than pyrene or 1-nitropyrene; at a dose of 2800 nmol, it induced liver tumors in 83% of the males and 7% of the females, with a lung tumor yield of 38 and 31%, respectively. Female mice treated with 200 nmol of 1,3-, 1,6- or 1,8-dinitropyrene did not develop liver tumors but the hepatic tumor incidence in males was 20, 32 and 16%, respectively, which was significantly greater than that found in mice treated with pyrene. In male mice administered 2800 nmol of benz[a]anthracene, the hepatic tumor incidence was 79%, while treatment with 7-nitrobenz[a]anthracene showed an incidence of only 28%. Similarly, 560 nmol of benzo[a]pyrene caused a 49% liver tumor yield in males while those given 6-nitrobenzo[a]pyrene had a 28% incidence. Treatment with benzo[a]pyrene also induced a 35 and 48% lung tumor incidence in males and females while the comparable values in 6-nitrobenzo[a]pyrene-treated mice were 14 and 2%. Chrysene administered at 2800 nmol per mouse induced hepatic and lung tumors in 41% and 21% of the males, respectively; at the 700-nmol dose, it induced only liver tumors in 29% of the males and in none of the females. In contrast, treatment with 6-nitrochrysene at 700 nmol per mouse resulted in a 76 and 23% hepatic tumor incidence in males and females, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)