Yukitada Miyata

Hepatocarcinogenicity of polychlorinated terphenyl (PCT) in ICR mice and its enhancement by hexachlorobenzene (HCB).

Studies were made on the carcinogenic effects of hexachlorobenzene (HCB) and polychlorinated terphenyl (PCT) singly and in combination when given orally to mice for 24 weeks. PCT alone induced liver tumors, nodular hyperplasias and hepatocellular carcinomas. HCB alone had no effect, but it enhanced the induction of liver tumors by PCT.

Pathological Analysis of the Carcinogenicity of Sodium o-Phenylphenate and o-Phenylphenol

Potential carcinogenicity and promoting effects of sodium o-phenylphenate (OPP-Na) in two-stage urinary bladder carcinogenesis were shown in male F344 rats pretreated with 0.01% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). However, o-phenylphenol (OPP) did not enhance the occurrence of urinary bladder lesions in rats pretreated with BBN. Scanning electron microscopy of OPP-Na-treated animals demonstrated a dose-dependent production of pleomorphic microvilli on the luminal surface of bladder superficial cells, whereas these were not observed with OPP. These results give some support to the conclusion that OPP-Na may be carcinogenic in the urinary bladder of male rats.

Effects of caffeine and saccharin on DNA in the bladder epithelium of rats treated with N-butyl-N-(3-carboxypropyl)-nitrosamine

The damage to DNA caused by N-butyl-N-(3-carboxypropyl)-nitrosamine (BCPN), saccharin and caffeine in the urinary bladder epithelium of female rats and its subsequent repair was investigated using alkaline sucrose density gradient analysis with a fluorimetric procedure for DNA determination and light and electron microscopy. Exposure of the bladder epithelium to 50 mg/kg body wt. of BCPN solution for 5 min resulted in serious damage of DNA within 2 h. Subsequent repair of most of the DNA damage, as indicated by reconversion of low molecular weight DNA fragments to larger ones, began after 6 h, and appeared to be complete after 48 h. Caffeine and saccharin induced no remarkable changes in the sedimentation profiles of DNA of the epithelial cells, with or without pretreatment of the cells with BCPN (administered to rats as 0.05% BCPN in the drinking water for 4 weeks). These results were confirmed by light and electron microscopy.

Effects of the co-mutagen norharman in rats☆

Abstract Studies were made on the acute and subacute toxic effects of the co-mutagen norharman when given orally to male Fischer strain rats. Animals were given diets containing 1500 ppm of norharman for 28 days, and 3 or 6 animals were killed for examination on days 0, 1, 3, 7, 14, 21, and 28. During norharman administration, the body weight and food and water intakes of the rats gradually decreased, the kidney weight increased significantly and blood urea nitrogen also increased. Norharman caused segmental coagulative necrosis of the tubular epithelium of the kidney, which increased in severity and extent with the period of treatment, but glomerular changes were negligible. In the testis, the germinal epithelium showed decreased spermatogenic activity after day 7. Norharman had no detectable effects on other organs.

Promoting effects of unilateral ureteric ligation on two-stage urinary bladder carcinogenesis in rats

The effect of ligation of the left ureter on the development of lesions in the urinary bladder were investigated in male F344 rats treated with 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) for 2 weeks followed by 0.002% N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) for 10 or 22 weeks. The lesions of the urinary bladder found in weeks 12 and 24 in rats treated with BBN and EHBN were preneoplastic papillary or nodular hyperplasia (PN hyperplasia), papilloma and cancer. The incidences and numbers of these lesions per 10 cm of basement membrane of urinary bladder were increased significantly by ureteric ligation. Treatment with BBN or EHBN only induced no remarkable change and thus the doses used were subcarcinogenic in the conditions used. The results show that unilateral ureteric ligation enhanced two-stage bladder carcinogenesis.