Rodriguez L V, Dunsford H A, Steinberg M, Chaloupka K K, Zhu L, Safe S, Womack J E, Goldstein L S
University of Texas M.D. Anderson Cancer Center, Department of Molecular Pathology, Houston 77030, USA.
Carcinogenesis. 1997 Jan;18(1):127-35. doi: 10.1093/carcin/18.1.127.
The present study determined tumorigenicity, tumor classification and DNA damage induced in infant mice by benzo[a]pyrene (B[a]P) or Manufactured Gas Plant (MGP) residues after a single exposure. Male and female B6C3F1 mice were exposed to B[a]P or MGP residue from a single environmental site (MGP-4) and males were also exposed to MGP residue composite from seven different sites (MGP-M7). At 26, 39 and 52 weeks after exposure tumorigenesis was assessed in lung, forestomach and liver. Formation and persistence of DNA adducts were quantified by 32P-postlabeling. Exposure of males to B[a]P induced liver tumors in a dose and time dependent manner. MGP induced more advanced tumors than B[a]P. Only a single liver tumor was found in MGP-4 treated females. No forestomach and few pulmonary adenomas were induced in males or females. MGP-4, MGP-M7 or B[a]P induced DNA adducts in males and females. Adducts in liver, lung and forestomach peaked on different days and decreased at different rates. At 24 h post-exposure, no significant differences in initial DNA adduct levels occurred in males and females exposed to MGP-4 or B[a]P. Lack of DNA damage (adducted DNA) did not account for non-responsiveness of lung and forestomach in B6C3F1 genders as well as in liver in females. MGP tumorigenicity could not be accounted for solely by B[a]P content nor did it reflect additivity of B[a]P and other carcinogenic polycyclic aromatic hydrocarbons (PAHs) in MGP. Synergy among MGP-PAHs, presence of unidentified carcinogens and/or promoters in MGP may account for MGP potency. The B6C3F1 infant male model is a convenient and rapid assay for assessing MGP liver tumorigenicity and potency.
本研究确定了苯并[a]芘（B[a]P）或人造煤气厂（MGP）残渣单次暴露后在幼鼠中诱发的致瘤性、肿瘤分类及DNA损伤。将雄性和雌性B6C3F1小鼠暴露于来自单一环境场所的B[a]P或MGP残渣（MGP-4），雄性小鼠还暴露于来自七个不同场所的MGP残渣混合物（MGP-M7）。在暴露后26、39和52周，评估肺、前胃和肝脏中的肿瘤发生情况。通过32P后标记法定量DNA加合物的形成和持久性。雄性小鼠暴露于B[a]P会以剂量和时间依赖性方式诱发肝肿瘤。MGP诱发的肿瘤比B[a]P更严重。在接受MGP-4处理的雌性小鼠中仅发现一个肝肿瘤。雄性或雌性小鼠均未诱发前胃肿瘤，肺腺瘤也很少。MGP-4、MGP-M7或B[a]P在雄性和雌性小鼠中均诱发了DNA加合物。肝脏、肺和前胃中的加合物在不同日期达到峰值，并以不同速率下降。在暴露后24小时，暴露于MGP-4或B[a]P的雄性和雌性小鼠的初始DNA加合物水平没有显著差异。缺乏DNA损伤（加合DNA）不能解释B6C3F1雌雄小鼠肺和前胃以及雌性小鼠肝脏的无反应性。MGP的致瘤性不能仅由B[a]P含量来解释，也不反映MGP中B[a]P和其他致癌多环芳烃（PAH）的加和性。MGP-PAH之间的协同作用、MGP中存在未鉴定的致癌物和/或促癌剂可能解释了MGP的效力。B6C3F1幼龄雄性小鼠模型是评估MGP肝致瘤性和效力的便捷快速检测方法。
