Effect of <i>Clonorchis sinensis</i> infection and dimethylnitrosamine administration on the induction of cholangiocarcinoma in Syrian golden hamsters

, Lee, J H; , Rim, H J; , Bak, U B

doi:1993.31.1.21

Korean J Parasito > Volume 31(1):1993 > Article

Original Article


Korean J Parasitol. 1993 Mar;31(1):21-30. English. Published online Mar 20, 1994. http://dx.doi.org/10.3347/kjp.1993.31.1.21
Copyright © 1993 by The Korean Society for Parasitology


Effect of Clonorchis sinensis infection and dimethylnitrosamine administration on the induction of cholangiocarcinoma in Syrian golden hamsters
Jae-Hyun Lee,¹Han-Jong Rim,^*¹ and Ung-Bok Bak²
¹Department of Parasitology and Institute for Tropical Endemic Diseases, College of Medicine, Korea University, Seoul 136-701, Korea.
²Department of Pathology, College of veterinary Medicine, Seoul National University, Suwon 441-744, Korea.

Received December 30, 1992; Accepted February 04, 1993.
Abstract
The study was carried out to observe the effects of Clonorchis sinensis infection on induction of cholangiocarcinoma in Syrian golden hamsters to which 15 ppm dimethylnitrosamine (DMN) solution was administered for 8 weeks. The histopathological changes of the bile duct and liver cells were observed at the 11th week. In six of 8 hamsters (75%) which were treated with DMN and then infected with C. sinensis, the livers developed cholangiocarcinoma at 10 weeks after the infestation of C. sinensis. The features of cholangiocarcinoma lesions were adenomatous or papillary hyperplasia of the bile duct epithelia showing distinct anaplastic changes with mucinous cell metaplasia and necrotic area. In the hamsters which received either DMN or C. sinensis alone, the livers showed only hyperplastic changes of the bile duct epithelial cells. It was suggested that C. sinensis infection and DMN administration could be a synergism on the development of cholangiocarcinoma in Syrian golden hamsters.

Figures


	Fig. 1 Changes of body weights in the hamsters. ↓ : P < 0.001, each group is significantly different from control group.


	Fig. 2 Average body weights and percent of liver weight to body weight in each group at the 11th week. ↓ : Percentages of gr. I and gr. II to gr. IV are significantly high (P < 0.001).

Figs. 3-6
Fig. 3. Cut surface of the liver of a hamster treated with DMN and C. sinensis shows gray-white masses (arrow heads) 0.2-0.5 cm in diameter. Fig. 4. Microscopic appearance of the liver of a hamster infected with C. sinensis shows the dilated bile duct containing the worm (C) and the hyperplasia of bile duct epithelia (arrow). Hematoxylin and eosin (HE) stains (× 100) Fig. 5. Microscopic appearance of the liver of a hamster treated with DMN shows adenomatous hyperplasia of bile duct epithelia. HE stains (× 200) Fig. 6. Microscopic appearance of the liver of a hamster treated with DMN and C. sinensis shows papillary proliferation of the epithelium. HE stains (× 100)

Figs. 7-8
Fig. 7. In high magnification of Fig. 6, the bile duct shows carcinomatous changes such as irregular stratification, pleomorphism and mitosis (arrow heads) of epithelial cells. HE (× 400) Fig. 8. Microscopic appearance of cholangiocarcinoma shows a lot of metaplastic goblet cells (arrows) in DMN plus C. sinensis group. Alcian blue and periodic acid Schiff stains (AB-PAS) (× 200)

Tables


	Table 1 Gross lesions of the liver of hamsters


	Table 2 Occurrence numbers for histological lesions of bile duct of hamsters in each group


	Table 3 Occurrence numbers of other histopathological changes of the livers in each group

References


1.	Bannasch P, et al. Z Krebsforsch 1971;76:193–215.

2.	Bannasch P, Massner B. [Fine structure of cholangiofibromas induced in the rat by n-nitrosomorpholine (author's transl)]. Virchows Arch B Cell Pathol 1977;24(4):295–315.

3.	Belamaric J. Intrahepatic bile duct carcinoma and C. sinensis infection in Hong Kong. Cancer 1973;31(2):468–473.

4.	Cayama E, Tsuda H, Sarma DS, Farber E. Initiation of chemical carcinogenesis requires cell proliferation. Nature 1978;275(5675):60–62.

5.	Cha SH, et al. Korea Univ Med J 1991;28(3):741–757.

6.	Ch'in KY, Lei AT, Wang TY. Primary mucinous carcinoma of liver associated with Clonorchis sinensis infection. Chin Med J 1955;73(1):26–35.

7.	Chung KN. J Busan Med Coll 1975;15(1):217–227.

8.	Chung CS, et al. Korean J Pathol 1976;10(1):33–46.

9.	Chung KS, et al. Ewha Med J 1987;10(2):69–81.

*10.*	Farber E. Similarities in the sequence of early histological changes induced in the liver of the rat by ethionine, 2-acetylamino-fluorene, and 3'-methyl-4-dimethylaminoazobenzene. Cancer Res 1956;16(2):142–148.

*11.*	Farber E, Sarma DS. Hepatocarcinogenesis: a dynamic cellular perspective. Lab Invest 1987;56(1):4–22.

*12.*	Flavell DJ. Liver-fluke infection as an aetiological factor in bile-duct carcinoma of man. Trans R Soc Trop Med Hyg 1981;75(6):814–824.

*13.*	Flavell DJ, Lucas SB. Potentiation by the human liver fluke, Opisthorchis viverrini, of the carcinogenic action of N-nitrosodimethylamine upon the biliary epithelium of the hamster. Br J Cancer 1982;46(6):985–989.

*14.*	Fong YY, Chan WC. Bacterial production of di-methyl nitrosamine in salted fish. Nature 1973;243(5407):421–422.

*16.*	Hecht SS, Hoffmann D. Tobacco-specific nitrosamines, an important group of carcinogens in tobacco and tobacco smoke. Carcinogenesis 1988;9(6):875–884.

*17.*	Hoeppli R. Chin Med J 1933;47:1125–1141.

*18.*	Hou PC. The pathology of Clonorchis sinensis infestation of the liver. J Pathol Bacteriol 1955;70(1):53–64.

*19.*	Hou PC. The relationship between primary carcinoma of the liver and infestation with Clonorchis sinensis. J Pathol Bacteriol 1956;72(1):239–246.

*20.*	Hou PC. Primary Carcinoma of Bile Duct of The Liver of the Cat (Felis Catus) Infested with Clonorchis Sinensis. J Pathol Bacteriol 1964;87:239–244.

*21.*	Chang HP. Hepatic Clonorchiasis and Carcinoma of the Bile Duct in a Dog. J Pathol Bacteriol 1965;89:365–367.

*22.*	Iida H. Jpn J Parasitol 1985;34:7–16.

*23.*	Kim YI. Liver carcinoma and liver fluke infection. Arzneimittelforschung 1984;34(9B):1121–1126.

*24.*	Kim YI, et al. J Korean Surg Soc 1968;10(4):273–281.

*25.*	Kim YI, et al. Seoul J Med 1974;15(3):247–255.

*26.*	Lee SY, Lee SH, Chi JG. [Ultrastructural Changes Of The Hepatocytes And Biliary Epithelia Due To Clonorchis Sinensis In Guinea Pigs]. Korean J Parasitol 1978;16(2):88–102.

*27.*	Lee SH, Shim TS, Lee SM, Chi JG. [Studies On Pathological Changes Of The Liver In Abino Rats Infected With Clonorchis Sinensis]. Korean J Parasitol 1978;16(2):148–155.

*28.*	Min HK, et al. Ewha Med J 1985;8(2):111–115.

*29.*	Min HK, et al. Yonsei Rep Trop Med 1986;17(1):1–10.

*30.*	Nakajima T, Kondo Y. Well-differentiated cholangiocarcinoma: diagnostic significance of morphologic and immunohistochemical parameters. Am J Surg Pathol 1989;13(7):569–573.

*31.*	Purtilo DT. Clonorchiasis and hepatic neoplasms. Trop Geogr Med 1976;28(1):21–27.

*32.*	Reddy KP, Buschmann RJ, Chomet B. Cholangiocarcinomas induced by feeding 3'-methyl-4-dimethylaminoazobenzene to rats. Histopathology and ultrastructure. Am J Pathol 1977;87(1):189–204.

*33.*	Rim HJ. Clonorchiasis in Korea. Korean J Parasitol 1990;28 Suppl:63–78.

*34.*	Sell S. Comparison of oval cells induced in rat liver by feeding N-2-fluorenylacetamide in a choline-devoid diet and bile duct cells induced by feeding 4,4'-diaminodiphenylmethane. Cancer Res 1983;43(4):1761–1767.

*35.*	Sell S, Dunsford HA. Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma. Am J Pathol 1989;134(6):1347–1363.

*36.*	Sher L, Iwatsuki S, Lebeau G, Zajko AB. Hilar cholangiocarcinoma associated with clonorchiasis. Dig Dis Sci 1989;34(7):1121–1123.

*37.*	Terao K, Nakano M. Cholangiofibrosis induced by short-term feeding of 3'-methyl-4-(dimethylamino)azobenzene: an electron microscopic observation. Gann 1974;65(3):249–260.

*38.*	Thamavit W, Bhamarapravati N, Sahaphong S, Vajrasthira S, Angsubhakorn S. Effects of dimethylnitrosamine on induction of cholangiocarcinoma in Opisthorchis viverrini-infected Syrian golden hamsters. Cancer Res 1978;38(12):4634–4639.

*39.*	Thamavit W, Kongkanuntn R, Tiwawech D, Moore MA. Level of Opisthorchis infestation and carcinogen dose-dependence of cholangiocarcinoma induction in Syrian golden hamsters. Virchows Arch B Cell Pathol Incl Mol Pathol 1987;54(1):52–58.

*40.*	Thamavit W, Moore MA, Hiasa Y, Ito N. Enhancement of DHPN induced hepatocellular, cholangiocellular and pancreatic carcinogenesis by Opisthorchis viverrini infestation in Syrian golden hamsters. Carcinogenesis 1988;9(6):1095–1098.

*41.*	Wykoff DE. Studies on Clonorchis sinensis. III. The host-parasite relations in the rabbit and observations on the relative susceptibility of certain laboratory hosts. J Parasitol 1958;44(5):461–466.