Title: | Different carcinogenic process in cholangiocarcinoma cases epidemically developing among workers of a printing company in Japan |
Author(s): | Sato Y; Kubo S; Takemura S; Sugawara Y; Tanaka S; Fujikawa M; Arimoto A; Harada K; Sasaki M; Nakanuma Y; |
Address: | "Department of Human Pathology, Kanazawa University Graduate School of Medicine Kanazawa, Japan. Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine Osaka, Japan. Artificial Organ & Transplantation Division, Department of Surgery, University of Tokyo Tokyo, Japan. Department of Surgery, Ishikiri Seiki Hospital Osaka, Japan. Department of Surgery, Nissay Hospital Osaka, Japan. Department of Hepato-Biliary-Pancreatic Surgery, Osaka Red Cross Hospital Osaka, Japan. Department of Human Pathology, Kanazawa University Graduate School of Medicine Kanazawa, Japan ; Department of Pathology, Shizuoka Cancer Center Shizuoka, Japan" |
ISSN/ISBN: | 1936-2625 (Electronic) 1936-2625 (Linking) |
Abstract: | "Recently, cholangiocarcinoma has epidemically developed among young adult workers of a printing company in Japan. Exposure to organic solvents including 1,2-dichloropropane and/or dichloromethane is supposed to be associated with the carcinoma development. The metabolism of dichloromethane proceeds through a Theta-class glutathione S-transferase (GST) T1-1-catalyzed pathway, where its reactive intermediates have been implicated in genotoxicity and carcinogenicity. This study examined features of the carcinogenic process of the cholangiocarcinoma developed in the printing company. Surgically resected specimens of the cholangiocarcinoma cases were analyzed, where all cases were associated with precursor lesions such as biliary intraepithelial neoplasia (BilIN) and/or intraductal papillary neoplasm of the bile duct (IPNB). Immunohistochemical analysis confirmed constitutional expression of GST T1-1 in normal hepatobiliary tract. Immunostaining of gamma-H2AX, a marker of DNA double strand break, showed that its expression was significantly increased in foci of BilIN, IPNB and invasive carcinoma as well as in non-neoplastic biliary epithelial cells of the printing company cases when compared to that of control groups. In the printing company cases, immunohistochemical expression of p53 was observed in non-neoplastic biliary epithelial cells and BilIN-1. Mutations of KRAS and GNAS were detected in foci of BilIN in one out of 3 cases of the printing company. These results revealed different carcinogenic process of the printing company cases, suggesting that the exposed organic solvents might act as a carcinogen for biliary epithelial cells by causing DNA damage, thereby contributing to the carcinoma development" |
Keywords: | "Adult Aged Animals Bile Duct Neoplasms/genetics/metabolism/*pathology Bile Ducts, Intrahepatic/*pathology Carcinogenesis/*chemically induced/genetics/pathology Carcinogens/toxicity Cholangiocarcinoma/genetics/metabolism/*pathology Chromogranins DNA Mutati;" |
Notes: | "MedlineSato, Yasunori Kubo, Shoji Takemura, Shigekazu Sugawara, Yasuhiko Tanaka, Shogo Fujikawa, Masahiro Arimoto, Akira Harada, Kenichi Sasaki, Motoko Nakanuma, Yasuni eng 2014/09/10 Int J Clin Exp Pathol. 2014 Jul 15; 7(8):4745-54. eCollection 2014" |