Centrilobular Distribution of Ethylnitrosourea-Induced Hepatocellular Foci in the Mouse / 대한간학회지

BACKGROUND/AIMS: Hepatocytes on the hepatic lobule mipate from portal zone to centrilobular mea as the DNA synthesis within it. And also, the xenobiotic reactions reveal characteristic differences associated with zone specific metabolism in the liver acinus. In this study, the zonal distribution of ethylnitrosourea (ENU)-induced hepatic precancerous lesion was stereologically investigated. METHODS: Nine B6C3F1 mices were given I.p. injection of ENU (60 ug/pn body weight) when the pups were 15 days old prior to sacrifices at 8 weeks of life. All the 150 consecutive sections, 3 p m in thickness, were stained with hematoxylin and eosin and identified the basophilic precancerous lesions with 80-165 p m diameter in equatorial plane by the Zeiss microprojector. And then the distances from the center of selected foci to terminal hepatic vein or portal vein branches were estimated under the microscopic fields. As a control group, the same estimations were performed from the random points by the appointments of random digit table. RESULTS: Mean distance between ENU-induced 52 hepatocellular foci and the nearest terminal hepytic vein was 181.15+112.39 p m (Mean+ SD), but that of randomly selected 104 points was 291.73+157.98pm (Mean+5D) (Students t-test, p<0.0005). Substantially, 52.7% of ENU-induced 52 hepatocellular foci were within 300 p m from the terminal hepatic vein, but randomly selected 104 points were only 50.9% (Shapiro Wilk W test, w=0.819857, p=0.048038). Mean distance from ENU-induced 52 foci to portal vein was 398.85+149.98pm (Mean+SD), but that from the randomly selected 104 points was 315.87+145.79 pm (Mean+SD)(Students t-test, p<0.0005). CONCLUSION: Stereologically, ENU-induced mice liver cell foci distribute non-randomly to Zone III, centrilobular zone of mouse hepatic acini where promote invasion toward terminal hepatic veins.

Periportal Distribution of Diethylnitrosamine-Induced Gamma-GTP Positive Foci in the Liver of Sprague-Dawley Rat / 대한간학회지

BACKGROUNR/AIMS: Heterogeneity of liver cell populations within the hepatic lobules can affect xenobiotic reaction. In this study, we attempt to clarify the stereological distribution of the y-GTP positive foci in hepatic lobule initiated by diethylnitrosamine and promoted by phenobarbital. METHODS/METERIALS: To the five Sprague-Dawley rats, one day after birth, diethylnitrosamine (0.15 pmole/pn) was intraperitoneally injected and by the weaning at four weeks of life, 0.035% phenobarbital in drinking water was fed for four weeks, at which time the rats were sacrified to obtain the livers. Livers were fixed in fresh cold ethanol acetic acid. Ihe 200 cotmecutive tissue sections were stained by histochemistry for y-GIP and countastained with toluidine blue ar HkE. Employing Zeiss microprojector, y-GTP foci wae traced. And then the largest cross-sectian (size class: 65-165 pm in diameter) of 52 y-GTP foci were selected. Using microscopic grid, distances fiom center of y-GlP foci to nearest centtal vein and bile ductule was measured. As a control group, out of 52 random points determined by rareken digit table, the distances were measured by the same romr. RESULT: the diameter Aom the central points of y-GIP positive foci to the neatest bile ductules was measured as 0.234620+0.14899mm (mean+SD) and the diameter from random points to the neatest bile ductules was measured as 0.303080+0.19582mm (mean+SD). Y-GTP positive foci located within 0.3mm diameter fram bile ductules were counted as 73.1% of 52 foci, whereas that of random points were only 55.8%. Accoring to Aequency table analysis by Shapiro-Wilk W test, there was significant difference by W-value (0.812065) and p-value (0.0144866). CONCLUSION: Stereologically, y -GTP positive foci initiated by diethylnitros;unine, promoted by phaxkarbital in neonatal Spague-Dawley rats were non-rarxlanly distributed in peripcetal atea (Rappaport zone I) in hepatic lobule during hepatocarcinogenesis.