Gen'i Murasaki

HISTOPATHOLOGICAL ANALYSIS OF PRENEOPLASTIC CHANGES DURING N-BUTYL-N-(4-HYDROXYBUTYL)- NITROSAMINE-INDUCED URINARY BLADDER CARCINOGENESIS IN RATS

Sequential microscopic alterations of the urinary bladder epithelium during carcinogenesis were examined in rats after oral administration of 0.01% or 0.05% N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine (BBN). Simple hyperplasia appeared after 4 weeks of BBN administration. This regressed by 12 weeks after BBN discontinuation but reappeared focally in some areas after 20 weeks and persisted to the termination of the experiment. Preneoplastic papillary or nodular hyperplasia appeared earlier and more frequently in rats treated with 0.05% BBN than in those treated with 0.01%, but these lesions regressed gradually during a prolonged observation period after BBN was discontinued. These results suggest that 2 types of papillary or nodular hyperplasias exist, one reversible and the other irreversible. Tumors appeared earlier in rats treated with 0.05% BBN than in those with 0.01% BBN.

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.

NEUROBLASTOMA IN SITU

Two cases of neuroblastoma in situ incidentally found in young infants at autopsy are reported. One was an 8‐day‐old female infant of large for dates clinically diagnosed as fetal erythroblastosis. Histologically, several foci of tumor were scattered within the medulla of the left adrenal gland. This case was thought to be multiple neuroblastoma in situ. The other was a 34‐day‐old male infant who was born premature and associated with patent ductus arteriosus (PDA). Grossly, a solitary small nodule was seen in the right adrenal gland. Microscopically, the lesion was located within the medulla. In both cases, the tumor was composed of lymphocyte‐like small and dark cells with rosette formations. Local infiltrations were observed, but not metastasis. The review of 611 autopsy cases of neuroblastoma reported in the Annual of the Pathological Autopsy Cases in Japan, vol. 11 (1968) to vol. 20 (1977)2 revealed 7 cases of neuroblastoma in situ including one of our cases. The peculiar features of neuroblastoma were described. ACTA PATHOL. JPN. 32: 537∼546, 1982.

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.

Effect of hepatotoxic or nephrotoxic agents on the induction of colon cancers in rats by 1,2-dimethylhydrazine.

Abstract The effects of liver injury induced by p,p′-diaminodiphenylmethane (DDPM) and of kidney injury induced by N-(3,5-dichlorophenyl)succinimide (NDPS) on 1,2-dimethylhydrazine (DMH) colon carcinogenesis were examined in rats. Prior administration of either DDPM or NDPS before DMH injection resulted in no significant differences in tumor incidences, but differences were noted in histological pattern, tumor size, and extent of invasion.