Waalkes M P, Diwan B A, Weghorst C M, Bare R M, Ward J M, Rice J M
Inorganic Carcinogenesis Section, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201.
Toxicol Appl Pharmacol. 1991 Sep 1;110(2):327-35. doi: 10.1016/s0041-008x(05)80015-8.
The B6C3F1 mouse liver has been widely used for the evaluation of carcinogenic or tumor promoting efficacy of various organic compounds, although little is known about the actions of metallic carcinogens in this system. Thus, the ability of cadmium to initiate or promote tumors in B6C3F1 mouse liver was studied. In promotion studies, diethylnitrosamine (DEN; 90 mg/kg, ip) was given as an initiator to 5-week-old mice followed 2 weeks later by 500 or 1000 ppm of cadmium in drinking water for 50 weeks. DEN caused an elevation of liver tumor incidence (13 tumor bearing mice/45 total) over control (1/48) which was prevented by cadmium (DEN + 500 ppm cadmium, 3/42; DEN + 1000 cadmium, 0/47). Cadmium alone did not further reduce the very low spontaneous liver and lung tumor incidence at approximately 1 year of age. DEN-induced lung tumor incidence (15/45) was also reduced by cadmium (DEN + 500 ppm cadmium, 11/42; DEN + 1000 ppm cadmium, 1/47) to control levels (0/48). In initiation studies, cadmium (20 or 22.5 mumol/kg, sc) was given to 5-week-old mice (n = 30-60) 2 weeks before an established promoting regimen of sodium barbital (BB) in drinking water at 500 ppm level was begun. Barbital in drinking water was given continuously for up to 92 weeks. Such cadmium doses caused acute, focal hepatic necrosis. Mice treated with BB and killed at 97 weeks of age showed an elevation of liver tumor multiplicity (7.44 tumors/liver) over control (2.24) that was prevented by cadmium in a dose-related manner (20 mumol/kg cadmium + BB, 3.93; 22.5 mumol/kg cadmium + BB, 1.87). Cadmium alone given by injection also reduced spontaneous liver tumor multiplicity. These results indicate that cadmium inhibits tumor formation in the B6C3F1 mouse liver initiation/promotion system regardless of route of exposure or sequence of administration. The possibility exists that cadmium has a specific toxicity toward previously initiated cells within liver and lung.
B6C3F1小鼠肝脏已被广泛用于评估各种有机化合物的致癌或促癌功效，尽管对于该系统中金属致癌物的作用了解甚少。因此，研究了镉在B6C3F1小鼠肝脏中引发或促进肿瘤的能力。在促癌研究中，将二乙基亚硝胺（DEN；90 mg/kg，腹腔注射）作为启动剂给予5周龄小鼠，2周后在饮用水中加入500或1000 ppm的镉，持续50周。DEN导致肝脏肿瘤发生率升高（13只荷瘤小鼠/45只总数），高于对照组（1/48），而镉可预防这种情况（DEN + 500 ppm镉，3/42；DEN + 1000 ppm镉，0/47）。单独使用镉并未进一步降低约1岁时极低的自发性肝脏和肺部肿瘤发生率。镉也将DEN诱导的肺部肿瘤发生率（15/45）降低至对照组水平（0/48）（DEN + 500 ppm镉，11/42；DEN + 1000 ppm镉，1/47）。在启动研究中，在开始既定的500 ppm水平的巴比妥钠（BB）饮用水促癌方案前2周，将镉（20或22.5 μmol/kg，皮下注射）给予5周龄小鼠（n = 30 - 60）。饮用水中的巴比妥持续给予长达92周。这样的镉剂量导致急性局灶性肝坏死。用BB处理并在97周龄处死的小鼠显示肝脏肿瘤多发性升高（7.44个肿瘤/肝脏），高于对照组（2.24），而镉以剂量相关方式预防了这种情况（20 μmol/kg镉 + BB，3.93；22.5 μmol/kg镉 + BB，1.87）。单独注射镉也降低了自发性肝脏肿瘤多发性。这些结果表明，无论暴露途径或给药顺序如何，镉均抑制B6C3F1小鼠肝脏启动/促癌系统中的肿瘤形成。镉对肝脏和肺中先前启动的细胞具有特异性毒性的可能性存在。
