Ultrastructural and immunohistochemical analysis of cholangiocarcinoma in immunized Syrian golden hamsters infected with Opisthorchis viverrini and administered with dimethylnitrosamine.
Utilizing the experimental model in Syrian golden hamsters, we explored the role of immunization in carcinogenesis. The animals, which were infected with liver flukes (Opisthorchis viverrini), and administered a subcarcinogenic dose of dimethylnitrosamine, developed cancer. Pre-immunizing with a crude somatic antigen did not reduce cancer development, but accelerated carcinogenesis. Histopathological analysis of the cancer tissues was done once at week 30 and again at week 39 using H and E staining, immunostaining for the p53 tumor suppressor phosphoprotein, and electron microscopy. Thirty weeks after immunization, the immunized hamsters developed tubular adenocarcinoma at a higher rate (71.43%) than the non-immunized group (20.00%). This rate (20.00%) increased to 63.64% by week 39. The small foci cancer in the non-immunized group decreased in frequency from 80.00% (at week 30) to 36.36% (by week 39), suggesting the small foci cancer progressed to tubular adenocarcinoma during the 9-week interval. Most of the observed tubular adenocarcinoma was well differentiated. Nearly all hamsters that tested positive for cancer also tested positive for p53 immunostaining in the epithelia of the small bile ducts. The positive reaction for p53-immunostaining was localized in the rough endoplasmic reticulum, Golgi apparatus and perinuclear membranes. The electron micrographs of these positive p53-immunostained cells showed characteristics of early cancer. The detection of p53 in early cancer development makes it a candidate as a tumor marker.
Tesana
S
S
Department of Parasitology, Faculty of Medicine, Khon Kaen University, Thailand.
Takahashi
Y
Y
Sithithaworn
P
P
Ando
K
K
Sakakura
T
T
Yutanawiboonchai
W
W
Pairojkul
C
C
Ruangjirachuporn
W
W
D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D002273:Carcinogens; D018281:Cholangiocarcinoma / Q000139:chemically induced / Q000276:immunology / Q000469:parasitology* / Q000473:pathology*; D003043:Cocarcinogenesis; D006224:Cricetinae; D004123:Dimethylamines; D007114:Immunization / Q000009:adverse effects*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000276:immunology / Q000469:parasitology* / Q000473:pathology*; D008297:Male; D008647:Mesocricetus; D016253:Microscopy, Immunoelectron; D009891:Opisthorchis / Q000276:immunology*
D000947:Antigens, Helminth; D002273:Carcinogens; D004123:Dimethylamines; C013962:dimethylnitramine