Modifying effects of 1,2-dichloropropane on N-nitrosobis(2-oxopropyl)amine-induced cholangiocarcinogenesis in male Syrian hamsters

Abstract

-Based on the findings of epidemiological studies in Japan that occupational exposure to 1,2-dichloropropane (1,2-DCP) was associated with increased cholangiocarcinomas, 1,2-DCP has recently been classified as being carcinogenic to humans (Group 1). However, the cholangiocarcinogenicity of 1,2-DCP has not been demonstrated experimentally, and it was negative for cholangiocarcinogenicity in rats and mice. The present study determined the effects of 1,2-DCP on N-nitrosobis(2-oxopropyl)amine (BOP)-induced cholangiocarcinogenesis in male hamsters. We found that 1,2-DCP did not enhance the development of BOP-induced atypical biliary hyperplasia and did not induce any lesions in liver bile duct when administered alone. Notably, 1,2-DCP had no effect on the proliferative activity of bile duct epithelial cells regardless of BOP-initiation. These results demonstrate that 1,2-DCP lacks promoting effects on BOP-induced cholangiocarcinogenesis and suggest the possibility that 1,2-DCP is not cholangiocarcinogenic to the hamster in the present model. In addition, 1,2-DCP also lacks promoting effects on pancreatic, lung, and renal carcinogenesis. As the occurrence of occupational cholangiocarcinomas in Japan might be attributed to exposure to multiple chemicals, the results of the present study indicate that it will be necessary to determine the cholangiocarcinogenic effects of concurrent exposure of 1,2-DCP and the other halogen solvents to which workers with cholangiocarcinomas were exposed.

Acute inhalation co‐exposure to 1,2‐dichloropropane and dichloromethane cause liver damage by inhibiting mitochondrial respiration and defense ability in mice

“…In 2013, the high incidence of bile duct cancer (cholangiocarcinoma) was first reported in workers at the offset color proof‐printing section of a printing company in Japan (Kumagai, Kurumatani, Arimoto, & Ichihara, ), which prompted more research about the carcinogenicity of 1,2‐DCP. Experimental studies revealed that gavage and inhalation of 1,2‐DCP caused bronchioloalveolar adenomas, carcinomas, nasal cavity tumors and Harderian gland adenomas in mice and rats (Gi et al, ; Kubo et al, ; Matsumoto, Umeda, Take, Nishizawa, & Fukushima, ; Toyoda, Takada, & Suzuki, ; Toyoda, Takada, & Suzuki, ). Based on the epidemiological data and toxicology studies on 1,2‐DCP, IARC reclassified 1,2‐DCP as a group 1 carcinogen (Benbrahim‐Tallaa et al, ; Kubo et al, ).…”