Centrilobular Distribution of Ethylnitrosourea-Induced Hepatocellular Foci in the Mouse

Kim, Byoung Hun; Lee, Soong Hwan; Yang, Seong Kyu; Kim, Jong Cheol; Cho, Yeong Jung; Jo, Yong Hyeon; Yoo, Byeong Moo; Jung, Chul Hun; Lee, Dong Hoo

Abstract

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.