Oncogenes in X-ray-transformed C3H 10T1/2 mouse cells and in X-ray-induced mouse fibrosarcoma (RIF-1) cells.

In order to better understand the molecular basis of X-ray induced carcinogenesis we have investigated RNA levels of oncogenes in an X-ray transformed C3H 10T1/2 fibroblast line (XTD) and RIF-1 cells isolated from an X-ray-induced fibrosarcoma in a C3H mouse. Steady-state levels of K-ras, H-ras, N-ras, abl, sis, src, and fos were unchanged in the X-ray-transformed cells compared with non-transformed C3H 10T1/2 cells. However, myc and raf mRNA levels were increased dramatically in the transformed cells.

Correlation of thyroid hormone dose-dependent regulation of K-ras protooncogene expression with oncogene activation by 3-methylcholanthrene: loss of thyroidal regulation in the transformed mouse cell.

Previously, it has been demonstrated that thyroid hormone is an important cofactor of the initiation of oncogenesis in vivo and in vitro. In order to determine the mechanism of thyroid hormone modulation of the initiation of carcinogenesis we have addressed the hypothesis that thyroid hormone regulates the expression of the critical protooncogene at the time of exposure to the carcinogen, and that the transcriptional activity of the protooncogene correlates with the ability of a carcinogen to "activate" the oncogene and thus modulate the subsequent transformation event. It has previously been shown that 3-methylcholanthrene transformation of C3H/10T1/2 mouse embryo cells in culture is the result of activation of the k-ras oncogene.

Thyroid hormone affects the expression of neoplastic transformation induced by DNA-transfection.

Thyroid hormone can dramatically modulate oncogenic transformation of cells in culture. To further investigate this we have used DNA-mediated gene transfer (transfection) to transform cells grown in the presence (+T3) or absence (-T3) of thyroid hormones. Removal of thyroid hormones from the culture media greatly reduced the appearance of transformed foci subsequent to transfection.

Induction of cytodifferentiation in C3H/10T1/2 mouse embryo cells by X-irradiation and benzo(a)pyrene.

5-Azacytidine has been reported to induce adipogenesis and myogenesis in C3H/10T1/2 mouse cells. Additionally, this agent will produce neoplastic transformation of C3H/10T1/2 cells. Very little other data is available regarding induction of differentiation by oncogenic agents.

Lowered superoxide dismutase activity in distant organs of tumor-bearing mice.

Solid tumors were induced by implantation of 5 X 10(6) Ehrlich carcinoma cells im into the right flank of 8- to 12-week-old female CBA/J mice. Tumor-bearing mice were killed at 0, 2, 4, 10, or 24 days after im implantation of the tumor cells, and superoxide dismutase (SOD) activities were determined in liver, spleen, kidneys, lungs, and leg muscle. Depressed SOD activities were seen in all organs studied.

Possible role of glutathione in the antitumor effect of a copper-containing synthetic superoxide dismutase in mice.

The effect of glutathione and a glutathione reductase inhibitor on the antitumor effect of Cu(II)(3,5-diisopropylsalicylate)2 (CuDIPS) was studied. CuDIPS is a low-molecular-weight copper coordination compound that exhibits superoxide dismutase-like activity. CuDIPS had antitumor activity against intraperitoneal Ehrlich ascites carcinoma in Swiss mice.

Pharmacologic activities of copper compounds in chronic diseases.

Copper complexes have been shown to be effective antiinflammatory, antiulcer, anticonvulsant, anticancer, and antidiabetic agents. This seemingly diverse variety of pharmacologic effects is unified by the hypothesis that copper complexes facilitate or promote tissue repair processes involving copper-dependent enzymes and that arthritis, ulcers, seizures, neoplasia, and diabetes are diseases of specific tissues in disrepair. The corollary to this hypothesis is that the loss or reduction of copper-dependent enzyme-mediated processes leads to tissue dysfunction that may be reversed with copper complex therapy.

Antitumor activity of picolinic acid in CBA/J mice.

The growth of a solid tumor induced by im implantation of Ehrlich ascites tumor cells in inbred CBA/J mice was retarded by treatment with an iron chelator, picolinic acid (PLA). Survival of the mice was also significantly increased after PLA treatment. However, the iron chelator deferoxamine had no such effects; tumor growth was slightly enhanced, and survival was decreased.

Antitumor effect of a copper coordination compound with superoxide dismutase-like activity.

Growth of Ehrlich carcinomas in inbred CBA mice was retarded by im administration of Cu(II)(3,5-diisopropylsalicylate)2 (CuDIPS). CuDIPS is a low molecular weight (mol wt = 503) copper coordination compound that exhibits superoxide dismutase (SOD)-like activity. It has been used as an anti-inflammatory agent and is lipid-soluble.

Superoxide dismutase activity of normal murine liver, regenerating liver, and H6 hepatoma.

By means of both direct assay and gel electrophoresis, normal A/J mouse liver was shown to possess both Cu-Zn and Mn superoxide dismutase (SD) activity. H6 hepatoma cells contained Cu-Zn SD activity, but no Mn SD activity was detectable. Isolated mitochondria from normal liver contained both forms of the enzyme, but isolated mitochondria from H6 hepatoma cells contained no SD activity.