The role of hepatic stimulator substance (HSS) on liver regeneration arrest induced by cadmium.
BACKGROUND
The mechanism of cadmium-induced liver regeneration arrest in relation to hepatic stimulator substance (HSS) biological activity was investigated.


METHODS
In Wistar rats subjected to 65 - 70% partial hepatectomy, saline, cadmium, cadmium and HSS were administered. The rats were also subjected to 30 - 34% partial hepatectomy. Mitotic index, immunochemistry for PCNA, 3[H]-thymidine incorporation into DNA and thymidine kinase activity were used as indices of liver regeneration. HSS biological activity was evaluated in all groups of rats using a bioassay.


RESULTS
Liver regeneration and HSS activity were arrested by cadmium during the first 24 h after partial hepatectomy. Both in normal and in cadmium-treated rats, the HSS activity was increased and liver regeneration coincided. HSS activity was stable in 30 - 34% hepatectomized rats. HSS administration was able to restore liver regeneration arrest induced by cadmium.


CONCLUSIONS
The biological activity of HSS increased at the time of G1/S transition of hepatocytes in the cell cycle and no increase was observed with asynchronous G1/S transition (30 - 34% partial hepatectomy). The suppression of HSS biological activity by cadmium seems to represent an important factor for liver regeneration arrest induced by the metal and HSS administration is able to restore liver regeneration.
Department of Experimental Pharmacology, Medical School, Athens University, 75 Mikras Asias St., Athens 115 27, Greece.
Konstantinos N
KN
Tzirogiannis
George K
GK
Papadimas
Kalliopi T
KT
Kourentzi
Vasiliki G
VG
Kondili
Christos D
CD
Androutsos
Rosa I
RI
Hereti
Maro I
MI
Triantaphyllou
Georgios I
GI
Panoutsopoulos
D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D006133:Growth Substances / Q000378:metabolism* / Q000494:pharmacology; D006498:Hepatectomy; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008934:Mitogens / Q000378:metabolism* / Q000494:pharmacology; D008940:Mitotic Index; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013937:Thymidine Kinase / Q000187:drug effects / Q000378:metabolism
D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008934:Mitogens; D010455:Peptides; D018809:Proliferating Cell Nuclear Antigen; C073456:hepatic stimulator substance; D002104:Cadmium; D004247:DNA; D013937:Thymidine Kinase