No abstract

The effect of phenobarbital (PB) on liver cells treated with 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) was studied using primary cultures of normal adult rat liver cells. Following a 1-day attachment period, primary liver cell cultures were treated with 0.24 mM 3'-Me-DAB for 6 days, and then treated with or without PB at 0.75, 1.5 and 3 mM for 19 days. Similarly, control cultures were treated with 0.5% dimethylsulfoxide (DMSO), a solvent for 3'-Me-DAB, for 6 days, and then treated with or without PB in the same way. Each treatment was done on 8 cultures. Chromosome analysis and cytochemical assay for gamma-glutamyltranspeptidase (GGT) activity were carried out on the carcinogen-treated and control cultures between 1 and 2 months after initiation of primary culture. Chromosomal abnormalities were detected in 23 of 32 carcinogen-treated cultures and also in 2 of 28 control cultures tested. However, GGT positive cells were detected only in the carcinogen-treated cultures at a frequency of 22/32. Of the 23 carcinogen-treated cultures with chromosomal abnormalities, 18 contained GGT positive cells. These results show a good correlation between chromosomal abnormality and acquisition of GGT activity at culture dish level. Furthermore, in the carcinogen-treated cultures, PB treatment caused a dose-dependent increase in the number of GGT positive cultures and in the percentage of GGT positive cells in each culture, and also caused a dose-dependent increase in the number of cultures with chromosomal abnormalities.

Eosinophilic gastroenteritis (EGE) can present findings on computed tomography (CT) images that resemble malignant tumors. EGE is generally treated with systemic oral steroid administration, which is reportedly effective in relieving symptoms at least temporarily. Here, we report a case of EGE that mimicked malignant lymphoma in a gastroduodenal lesion, in which treatment with a potassium-competitive acid blocker without systemic oral steroid administration relieved the symptoms and reversed the initial image findings. A 56-year-old woman became aware of discomfort in her epigastric region, which gradually worsened. This case showed antroduodenal wall thickness, which mimicked a malignant lymphoma with increased F-18 fluorodeoxyglucose (FDG) uptake by positron emission tomography/computed tomography (PET/CT). An upper gastrointestinal endoscopy revealed protruding erosions in the antrum and severe edematous changes in the duodenum. Extensibility of the normal gastric wall by insufflation also occurred. However, an abdominal ultrasound indicated wall thickening with a preserved wall structure. Histological examinations showed a large amount of eosinophil infiltration, mainly in the gastroduodenal mucosa, without malignant cells. Thus, we made a final diagnosis of EGE. The patient was then administered 20 mg vonoprazan fumarate per day because she refused steroid treatment and because the pathological lesion was also localized from the duodenum to the antrum. After 3 weeks of potassium-competitive acid blocker treatment, her symptoms were alleviated, and the degree and extent of thickening of the gastroduodenal wall in upper gastrointestinal endoscopy and ultrasonographic image findings had remarkably improved.

After treatment with 1.5 mM phenobarbital (PB) for about 2 months, non-tumorigenic rat liver epithelial-type cell lines (6F-7 and 6G-5), which were initiated by 3'-methyl-4-dimethyl-aminoazobenzene (3'-Me-DAB) in primary culture, showed an increase in plating efficiency, growth in soft agar and production of tumors in syngeneic animals. However, the PB-untreated control cells exhibited neither growth in soft agar nor production of tumors. Gamma-glutamyltranspeptidase (GGT)-positive (6F-7-cl-7) and negative (6F-7-cl-8) colonial clones, which were derived from 6F-7 cells, were also treated with 1.5 mM PB for about 2 months. The growth of GGT-positive 6F-7-cl-7 cells was not suppressed but rather stimulated by PB at 1.5 mM, whereas that of GGT-negative 6F-7-cl-8 cells was severely inhibited. Furthermore, the PB-treated 6F-7-cl-7 cells produced tumors in syngeneic animals, but the PB-treated 6F-7-cl-8 cells produced no tumors. The spontaneous cell line 6A-6, which was derived from the 3'-Me-DAB-untreated primary liver cell culture and was GGT-negative, did not exhibit tumorigenicity after treatment with 1.5 mM PB for the same period of time as described above. In conclusion, PB treatment efficiently and rapidly promoted the 3'-Me-DAB-initiated cells to a malignant state.

Collagenase-liver-perfusion technique, currently used with adult rat liver, was applied to isolation of hepatocytes from suckling rat liver. The total hepatocyte numbers isolated from suckling rats by collagenase-liver-perfusion technique were 9-fold higher than those by non-perfusion technique. The yield and viability of isolated hepatocytes from suckling rats were 18.1 X 10(7) cells per gram liver and 95%, respectively. The cell yield per gram liver and viability from suckling rats were 185% and 112% of those from adult ones, respectively. In comparison with adult rat hepatocytes, suckling rat hepatocytes were smaller and more homogeneous. The percentage (3.1%) of binucleate cells in the hepatocytes isolated from suckling rats was about one tenth of that (30.7%) in the hepatocytes isolated from adult rats. The isolated suckling rat hepatocytes had higher tyrosine aminotransferase (TAT) and glucose-6-phosphate (G6Pase) activities than adult ones. Suckling and adult rat hepatocytes were transferred to primary culture to compare their cell number kinetics and functional longevities. The functional longevities of those hepatocytes were assessed by their capacity to secrete albumin and alpha-fetoprotein (AFP) into the culture medium and to express TAT and G6Pase activities up to day 6 of primary culture.