Promotion of N-nitrosodimethylamine-initiated bile duct carcinogenesis in the hamster by the human liver fluke, Opisthorch is viverrini

Abstract

Four groups of male golden Syrian hamsters were treated as follows: Group I received 50 Opisthorchis viverrini metacercariae followed 41 days later by a single oral dose of 1.6 mg N-nitrosodimethylamine (NDMA), Group U received a single oral dose of 1.6 mg NDMA followed 96 h later by 50 O. viverrini metacercariae, Group III received a single oral dose of 1.6 mg NDMA only and Group IV 50 O. viverrini metacercanae only. Mortality was highest in Group I and II animals receiving both NDMA and parasites. Cholangio-carcinomas were discovered in five animals from Group I and in nine animals from Group II representing tumour incidences of 10% and 20%, respectively. None of the animals given NDMA alone (Group III) or parasites alone (Group IV) developed malignant bile duct tumours. The mean tumour latency period for Group I was 249 days (range 124–346 days) and for Group II 308 days (range 184–393 days). The difference for tumour latency between these two groups was not significant. Tumour was most frequently found in the right liver lobe, the lobe in the hamster which also contains the largest proportion of infecting O. viverrini worms. These results clearly indicate that an O. viverrini infection in the hamster host is capable of promoting NDMA-initiated bile duct carcinogenesis. These observations may bear some direct relevance to cholangiocarcinoma arising in association with Oriental liver fluke infection in man and may provide a useful tool for the study of an initiation-promotion system of aetlological significance for man.