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Relationship of histochemically detectable altered hepatocyte foci to hepatic tumorigenesis

Conference ·
OSTI ID:5660855
A new experimental system was used to examine the stages of chemically induced hepatic neoplasia in the rat. The treatment protocol involved the intraperitoneal injection of a single nonnecrogenic dose of carcinogen (diethylnitrosamine (DEN) or benzo(a)pyrene (BAP)) into male and female rats within one day after birth, followed by dietary exposure to promotor (0.05% dietary phenobarbital) beginning at weaning. Rat livers were examined for tumors and for foci of altered hepatocytes using six histochemical markers. Foci containing between one and six markers were identified and their average sizes were calculated. The same complement of histochemical tests was applied to the primary hepatic tumors observed in this study. The data showed that (1) The new treatment protocol was highly efficient for foci and tumor production. (2) Foci growth rates and incidence levels were directly related to hepatocarcinogenic effectiveness (DEN > BAP), whereas both carcinogens had similar effects on foci phenotypic properties. (3) After their formation, foci at a given level of phenotypic complexity did not become progressively more complex. (4) Foci incidence levels were sex dependent (females > males) but foci growth rates were the same for both sexes. (5) Foci growth rates and growth capacities were directly related to foci phenotypic complexity levels. (6) Foci frequencies and phenotypic complexities were inversely related; the reverse was true for tumors, although 10% of the tumors were relatively simple (3 markers or less). (7) Marker frequency distribution patterns were completely different in foci and tumors. From these observations we suggest that the foci are manifestations of the carcinogenic stimulus on control of cell division and phenotypic character.
Research Organization:
Argonne National Lab., IL (USA); Chicago Univ., IL (USA). Dept. of Radiology
DOE Contract Number:
W-31109-ENG-38
OSTI ID:
5660855
Report Number(s):
CONF-8305135-1; ON: DE84000570
Country of Publication:
United States
Language:
English