Kurata Y, Diwan B A, Ward J M
Tumour Pathology and Pathogenesis Section, National Cancer Institute, Frederick, MD.
Food Chem Toxicol. 1992 Mar;30(3):251-9. doi: 10.1016/0278-6915(92)90041-i.
The renal tumour-initiating activity of potassium bromate (KBrO3), a known genotoxic rat renal carcinogen, was investigated in male F344/NCr rats. 6-wk-old rats were given KBrO3 intragastrically as a single dose of 300 mg/kg body weight, which was confirmed by our preliminary toxicity study as a maximum tolerated single dose for this strain of rat. Starting 2 wk after KBrO3 treatment, groups of 39 rats received either a basal diet or a diet containing 4000 ppm barbital sodium (BBNa) as a promoting regimen and were killed at 30, 52, or 104 wk. Control rats received either dietary BBNa (4000 ppm) or the basal diet alone from wk 2 to 52 or 104 wk. Nephropathy was observed in all rats treated with KBrO3 followed by BBNa at 30 wk and in rats receiving BBNa alone, but not in rats exposed to KBrO3 alone. Dysplastic renal tubular cell foci (DTF), putative preneoplastic renal tubular cell lesions were found associated with nephropathy in rats exposed to KBrO3 followed by BBNa from 47 wk. The incidences and multiplicities of DTF and renal tubular cell tumours observed from 31 to 104 wk revealed no initiating effect of KBrO3 treatment. These results indicate that the KBrO3 dose of 300 mg/kg did not initiate renal carcinogenesis.
已知具有基因毒性的大鼠肾致癌物溴酸钾(KBrO₃)的肾肿瘤引发活性,在雄性F344/NCr大鼠中进行了研究。6周龄的大鼠经口给予KBrO₃,单剂量为300mg/kg体重,我们的初步毒性研究证实该剂量是此品系大鼠的最大耐受单剂量。在KBrO₃处理后2周开始,每组39只大鼠分别给予基础饮食或含4000ppm巴比妥钠(BBNa)的饮食作为促癌方案,并在30、52或104周时处死。对照大鼠从第2周到52周或104周单独给予饮食BBNa(4000ppm)或基础饮食。在30周时,所有先给予KBrO₃然后给予BBNa处理的大鼠以及单独给予BBNa的大鼠中均观察到肾病,但仅暴露于KBrO₃的大鼠未出现肾病。从47周起,在接受KBrO₃然后给予BBNa处理的大鼠中,发现发育异常的肾小管细胞灶(DTF),即假定的肾肿瘤前体细胞病变与肾病有关。在31至104周观察到的DTF和肾小管细胞瘤的发生率及数量表明,KBrO₃处理没有引发作用。这些结果表明,300mg/kg的KBrO₃剂量不会引发肾癌发生。