Hepatic toxicity of nickel chloride in rats.

Enhanced lipid peroxidation was observed in livers of rats killed 24 hr after sc injection of nickel chloride (NiCl2) (750 mumol per kg), as evidenced by 13-fold increase of conjugated dienes in microsomal lipids and 4-fold increase of thiobarbituric acid (TBA) chromogens in hepatic cytosol. Histologic examination of livers from rats killed one to three days after NiCl2 injection (500 mumol per kg) showed microvesicular fatty metamorphosis, mild hydropic degeneration, and foci of inflammation. Microvesicular steatosis of hepatocytes was confirmed by electron microscopy. Dose-related increases of serum aspartate aminotransferase (ALT) activity (up to 7-fold vs controls) and alanine aminotransferase (ALT) activity (up to 3-fold vs controls) were observed 24 hr after injection of NiCl2 (125 to 750 mumol per kg); diminished serum alkaline phosphatase activity (up to 72 percent reduction vs controls) was seen at NiCl2 dosages from 375 to 750 mumol per kg. Diethyldithiocarbamate did not influence the effects of NiCl2 on TBA-chromogens in liver homogenates or on serum AST and ALT activities but acted synergistically with NiCl2 to diminish serum alkaline phosphatase activity and to increase serum bilirubin concentration. This study demonstrates that parenteral administration of NiCl2 to rats produces acute hepatic toxicity, with enhanced lipid peroxidation, microvesicular steatosis, and increased serum AST and ALT activities.

In vitro migration of tumor cells from human neoplasms: inhibition by lymphokines.

We have previously described a noncytotoxic lymphokine, TMIF, with the capacity of inhibiting the in vitro migration of a variety of serially passaged experimental animal tumors, but not non-neoplastic cells. In the present study, we describe conditions for the assay of human tumor cell movement utilizing agarose microdroplets. Using this procedure, we were able to demonstrate that TMIF is as effective in inhibiting the in vitro migration of suspensions of tumor cells obtained from spontaneous human neoplasms, as it is in inhibiting model tumor systems. This finding demonstrates that responsiveness to TMIF is not merely a property conferred on tumor cells by prior serial passage. Also, by demonstrating that tumors of human origin are responsive, the present study raises the possibility that studies of TMIF in neoplastic disease may provide information of prognostic value. Also, they provide the hope that if TMIF proves therapeutically effective in animal models, those results may be translated to human disease.

Lymphokine-induced migration inhibition of murine tumor cells derived from solid neoplasms.

We have previously described a noncytotoxic lymphokine, tumor migration inhibition factor, with the capacity of inhibiting the in vitro migration of a variety of tumor cells maintained by animal passage in ascitic form. In the present study, we demonstrate that it is possible to prepare viable, motile tumor cell suspensions from solid tumors and that those cells migrate better than cells that had been propagated in ascitic form. Such preparations derived from solid tumors are inhibited by tumor migration inhibition factor to a degree comparable to that achieved with cells from ascitic tumors. Comparative studies utilizing a methylcholanthrene-induced fibrosarcoma as well as solid and ascitic forms of P815 mastocytoma and Ehrlich tumor demonstrate that responsiveness to tumor migration inhibition factor is not merely a property conferred upon tumor cells by prior animal passage in suspension. These results provide a further suggestion that the capacity for lymphokine-induced migration inhibition is a general property of tumor cells. This in turn raises the possibility that this capacity might vary in a predictable manner with malignant potential.