Ethanol이 Aflatoxin B1에 의해 유발되는 백서 간 전종양성 병변에 미치는 영향 = The Effect of Ethanol on Aflatoxin B1 Induced Preneoplastic Lesions in Rat Liver

다국어 초록 (Multilingual Abstract)

This study attempts to elucidate whether ethanol alters aflatoxin B1 (AFB1) induced experimental preneoplastic lesions. A total of 86 Sprague-Dawley male rats were used in the experiment and were divided into four groups : the control group, the ethanol treated group, the AFB1 treated group and the ethanol + AFB1 treated group. Ethanol(2.5g/kg) was administered daily together with the simultaneous administration of AFB1 (1mg/kg) at one hour intervals, using a nasogastric tube, two times per week, for 12 weeks. The control group was given a similar volume of distilled water or dimethylsulfoxide(DMSO). DMSO used to dissolve the AFB1(1mg AFB1 to 0.1ml DMSO). The animals were sacrificed at the 4th, 8th and 12th week of the experiment. Changes were observed using light microscopy, electron microscopy, immunohistochemical staining, and serum enzyme tests.
The followings are the results:
Light microscopically, the normal hepatic lobular structures were distorted and replaced by altered foci at the fourth experimental week, and then were replaced by basophilic nodules, eosinophilic nodules, clear to vacuolated nodules, and hyperplastic areas at the 8th or 12th experimental week.
The hyperplastic areas were distinct from the discrete basophilic, vacuolated, and eosinophilic nodular lesions compressing the surrounding parenchyma.
There was a decrease in the intensity of the PAS staining in the nodules, compared with that of the control.
Electron microscopically, the ethanol-only treated group showed proliferation of smooth endoplasmic reticulum(SER) and accumulation of lipid vacuoles at the 4th and 8th experimental week, and the degree of these changes became severe at the 12th experimental week, with deposition of collagen fibers.
The AFB1-treated group showed variations in the size and form of the mitochondriae, shortened or depleted microvilli, proliferation or blebbing of the SER, disorganization of the rough endoplasmic reticulum, free ribosomes, irregularly shaped nuclei and nuclear membrane, and nucleolar segregation of fibrillar and granular elements. These changes varied depending on experimental weeks and the degree of severity was proportional to the experimental duration. Also, these changes was more severe in the ethanol + AFB1 treated group, compared with those of the AFB1-only treated group.
Serum enzymes such as ALT, AST, ALP, TG, and GGT increased in the ethanol or AFB1 treated group, compared with those of the control group. These enzyme values were higher in the ethanol + AFB1 treated group than those in the AFB1 only treated group.
The glutathione S-transferase placental form positive(GST-P +) hepatic foci were prominent in the AFB1 or ethanol + AFB1 treated group, although they were not seen in the control group. They were scored by comparing the areas(mm^(2)) per cm^(2) of GST-P + foci in the liver with those of the corresponding control group. Among the experimental groups, the values were highest in the ethanol + AFB1 treated group. Also, the altered foci on the H & E slides were at the same sites as the GST-P positive areas.
The above results suggest that the glutathione S-transferase placental form positive(GST-P +) hepatic foci are subjectively useful markers for morphologic preneoplastic lesions, and that the ethanol exacerbated the GST-P + areas of the AFB1-induced preneoplastic lesions.