Carcinogenic effect of the 3-di-(hydroxymethyl-)amino-6-(5-nitro-2-furylethenyl-)1,2,4-triazines in Panfuran-S on mice]

The carcinogenic activity of Panfuran-S containing 3-di-(hydroxymethyl-)amino-6-(5-nitro-2-furylethenyl-)1,2,4-triazine (DHNT) orally administered to mice for 35 weeks was studied. DHNT produced malignant tumors of the forestomach in the highest incidence and also, in decreasing order of frequency, of the duodenum and/or jejunum, esophagus and urinary bladder. Forestomach squamous cell carcinomas were produced dose-dependently in mice receiving more than 350 ppm DHNT and rose to 100% in mice receiving 3,500 ppm. The incidence of duodenal and/or jejunal adenocarcinomas were 8 of 28 mice (29%) receiving 1,750 ppm and 10 of 17 mice (59%) receiving 3,500 ppm. The incidence of esophageal squamous cell carcinoma was 3 of 11 mice (11%) receiving 1,750 ppm and that of urinary bladder transitional cell carcinoma was 2 of 28 mice (7%) receiving 1,750 ppm and 1 of 17 mice (6%) receiving 3,500 ppm DHNT.     

Treatment of wounds from animals suspected of carrying neurotropic viruses.

The methods used at the Clinical Research Centre, Northwick Park Hospital, to treat wounds potentially infected with neurotropic viruses are outlined. Emphasis is laid on first aid and on surgical attention. Patients should remain under medical supervision for at least four weeks after the injury, the need for specific post-exposure treatment depending on the nature of the exposure.     

Development of hepatocellular carcinoma following treatment with6-mercaptopurine for ulcerative colitis: investigation of chromosomal aberration by comparative genomic hybridization

In a 64-year-old man who had been treated with prednisolone (PSL) and 6-mercaptopurine (6MP) for a long period, for ulcerative colitis (UC), hepatocellular carcinoma (HCC) was detected incidentally. The UC was in remission with these medications. After he had been taking these medications for about 8 years, HCC was detected by computed tomography (CT), done for the evaluation of an other disease. Blood chemistry examination results were normal, except that the protein induced by vitamin K antagonist (PIVKA)-II level was 7940 AU/ml. We performed resection of liver segment V. With comparative genomic hybridization, chromosomal aberrations were recognized; these were gains of 1q, 3ptel-21, 8p12, and 22q11.23–22q13.1. Generally, HCC is associated with hepatitis virus infection in most cases, but in this patient, the HCC was not related to hepatitis C virus (HCV) or HBV. It is presumed that this case was related to the immunosuppressive therapy for UC and was associated with the gains of 1q, 3p, and 8p.     

Possible enhancing effects of atrazine on growth of 7,12-dimethylbenz(a) anthracene-induced mammary tumors in ovariectomized Sprague-Dawley rats

Atrazine, one of the most commonly used herbicides in the world, has been reported to have endocrine disrupting effects in vivo. In the present experiment, influence of dietary atrazine on the late promotion/progression stage of mammary carcinogenesis in ovariectomized female Sprague-Dawley rats was examined after a single intragastric administration of 7,12-dimethylbenz(a)anthracene (DMBA). When the incidence of palpable mammary tumors reached about 50%, the animals were subjected to ovariectomy and divided into tumor bearing [DMBA-Tumor(+)] and non-tumor bearing [DMBA-Tumor(-)] groups, with subgroups of each fed a soybean-free diet containing 0, 5, 50, or 500 p.p.m. atrazine for 34 weeks. At the completion of the study, the tumor volume in the 50 and 500 p.p.m. treatment Tumor(+) subgroups was greater than in the 0 p.p.m. control case. In the DMBA-Tumor(-) group, higher incidences and volumes of the mammary tumors, with or without statistical significance (P <0.05), were observed in the 50 and 500 p.p.m. subgroups. Atrazine treatment tended to increase proportion of estrogen receptor alpha-positive tumors and stimulated cell proliferation in the DMBA-Tumor(+) group, but with no clear effects on serum hormone levels. The present study indicates that atrazine has a potential for enhancing the growth of mammary tumors, partly through increasing cell proliferation in the promotion/progression stage in female rats under ovarian hormone-free conditions.     

Ameloblastoma induces osteoclastogenesis: a possible role of ameloblastoma in expanding in the bone

Ameloblastoma, a tumor located in bone, when neglected, can perforate the bone and, ultimately, spread into the soft tissues. To expand in the bone, ameloblastoma must have a mechanism of resorbing the surrounding bone. However, the mechanism for bone resorption is poorly understood. In the present study, we found that RANKL and TNFalpha were expressed and secreted by ameloblastoma cells, and was proven to induce osteoclastogenesis. Our present results also showed that phosphorylation of p38, SAPK, p44/42 and Akt were upregulated under treatment of 10xCM (concentrated conditioned media of AM-1 cells). We also noticed formation of resorption lacunae on dentin slice by 10xCM-induced osteoclast-like MNCs. These results suggested that ameloblastoma by secreting RANKL and TNFalpha could induce osteoclastogenesis.