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TGF
is differentially expressed in liver foci induced by diethylnitrosamine initiation and peroxisome proliferator promotion
Chemical Industry Institute of Toxicology P0 Box 12137, Research Triangle Park, NC 27709, USA
1To whom correspondence should be addressed
Transforming growth factor 
(TGF) is a mitogenlc growth factor for hepatocytes that may play a role In the development of liver cancer in rodents and humans. Epidermal growth factor receptor (EGFR) is the receptor for TGF; its expression is also altered in mltogenic and carcinogenic processes. Homogeneous basophilic foci (HBF), the precursor lesion to hepatocellular carcinomas in peroxisome proliferator (PP)-treated rats, have labeling Indices much greater than surrounding liver ({small tilde}5- to 20-fold) and other types of foci ({small tilde}.2-fold greater than eosino philic foci; EF). To test the hypothesis that PP-induced HIBF over-express TGF and/or EGFR, male F344 rats were treated with the PP WY-14, 643 for 22 weeks (1000 p.p.m. in the diet) with (DEN-WY) and without (WY) prior diethylnitrosamine initiation (150 mg/kg body wt i.p.). Serial paraffin sections of liver were stained for TGF or EGFR and with hematoxylin and eosin. DEN-WY and WY abrogated the small amount of centrilobular TGF staining observed in livers from control rats. Increased staining for TGF was not observed in HBF induced by WY (0/22) or DEN-WY (0/101). Additionally, Increased EGFR expression was not observed in HBF Induced by WY (0/22) or DEN-WY (0/19) or in EF induced by DEN-WY (0/30). An unexpectedly large proportion of EF induced by DEN-WY (6/38) and DEN-control (3/11) were TGF-positive. None of the tumors Induced by WY (0/13) or DEN-WY (0/11) over-expressed TGF. All 13 WY-induced tumors also lacked increased expression of EGFR. TGF overexpression noted in a significant propor tion of EF was associated only with those regimens including DEN Initiation. In conclusion, TGF or EGFR overexpression is not associated with early appearing, rapidly proliferating HBF or tumors induced by PP.
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