Strong promoting effect of Opisthorchis viverrini infection on dimethylnitrosamine-initiated hamster liver

Abstract

Continuous administration of dimethylnitrosamine (DMN) to Syrian hamsters infected with the liver fluke, Opisthorchis viverrini (OV) results in a 100% incidence of cholangiocellular carcinomas. In a two-stage experiment, however, dosing with liver flukes caused only a few lesions to develop (Flavel, D.J. and Lucus, S.B. (1983) Carcinogenesis, 4, 927]. To clarify this anomaly, Syrian hamsters were initiated with 20 mg/kg DMN injected i.p. 19 days prior to 80 OV metacercaria infection. At 45 weeks, the animals receiving both DMN and the parasite demonstrated a 44% incidence of cholangiocarcinomas, a 93% incidence of cholangiofibrosis, a 35% incidence of mucous cystadenomas and a 98% incidence of hepatocellular nodules with an average number of 9.1 +/- 4.1 per animal. Animals receiving DMN alone developed 85% hepatocellular nodules with an average number of only 3.0 +/- 2.7 and no bile duct lesions. In the parasite alone group, only cholangiofibrosis was detected in a few animals and no lesions were encountered in untreated controls. These results thus demonstrate that the post-initiation influence of Opisthorchiasis is indeed effective in promoting the development of both cholangiolar and hepatocellular lesions initiated by DMN.