Ornithine Decarboxylase Activity In Mice Research Articles

Induction of epidermal ornithine decarboxylase activity in mouse skin exposed to biogenic silica fibers.

The present study demonstrates that biogenic silica fibers (BSF), previously shown to promote skin tumors in mice and more recently to promote the induction of mesotheliomas when injected into the pleural cavity of rats, rapidly induces epidermal ornithine decarboxylase (ODC) activity in SENCAR mice following topical application. The time course for induction of epidermal ODC by BSF was very similar to that observed following topical treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). Maximal ODC activity was observed 4-6 h following treatment with BSF. Cycloheximide (70 mg/kg i.p.) partially inhibited (61%) the induction of ODC by BSF at 5 h. In addition, retinoic acid (RA, 5 micrograms per mouse given 30 min before BSF) effectively inhibited BSF-induced ODC by 68%, while indomethacin (100 micrograms per mouse 2 h before BSF) had little or no effect. Copper(II) bis(diisopropylsalicylate) (2 mumol 30 min before BSF), an effective inhibitor of TPA-induced ODC activity and tumor promotion, also had little or no effect on BSF-induced ODC. The work described in this paper suggests that BSF induces epidermal ODC by a very specific mechanism that exhibits both similarities and differences with that of the phorbol ester, TPA. Nevertheless, this response strongly supports the conclusion that BSF is an effective tumor promoter in mouse skin and that ODC induction is an integral part of the mechanism of action of this environmental promoter.

The Effect of Tumor Burden on Ornithine Decarboxylase Activity in Mice

Polyamines are essential for cell growth of normal and neoplastic tissue, alpha-Difluoromethylornithine (DFMO) is a known irreversible inhibitor or ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. The purpose of this study was to examine the effects of tumor burden on ODC in tissues of tumor-bearing compared with tumor-free mice. Twenty-eight male Balb/c mice were divided into four groups of 7 each. Groups 1 and 2 were inoculated subcutaneously with 10 x 10(6) MC-26 mouse colon adenocarcinoma cells. Groups 3 and 4 were kept as tumor-free controls. Ten days after inoculation, groups 2 and 4 were injected with DFMO (200 mg/kg) intraperitoneally (IP) while Groups 1 and 3 received saline. Two hours after the injection of DFMO the animals were sacrificed. The tumor, pancreas, kidney, and liver were excised and analyzed for ODC activity. DFMO caused a significant reduction (compared with controls that did not receive DFMO) in the ODC activity of tumors; however, ODC activity of the kidney, pancreas, and liver of tumor-bearing mice was not affected. Additionally, the basal ODC activity in the kidney, liver, and pancreas of tumor-bearing mice was significantly lower compared with tumor-free controls. DFMO lowered ODC activity in the kidney, pancreas, and liver of tumor-free mice. These results suggest that the presence of MC-26 tumor causes systemic effects that alter ODC activity and the response to a known inhibitor of ODC.

Influence of dietary menhaden oil upon carcinogenesis and various cutaneous responses to ultraviolet radiation.

Abstract Recent reports suggest that eicosapentaenoic acid (EPA) inhibits growth of transplanted tumors and the formation of various chemically induced cancers in animals. Menhaden oil is a source of polyunsaturated lipid with a high content of EPA, an omega‐3 fatty acid. We sought to explore the effects of menhaden oil on photocarcinogenesis by employing the hairless mouse/UV‐carcinogenesis model. Five groups of 40 SKH‐Hr‐1 mice received (a) a semipurined equicaloric diet containing either 0.75% corn oil, 4% corn oil. 4% menhaden oil or 12% menhaden oil and (b) an escalating regimen of UV radiation to a cumulative dose of 70 J/cm2. Additional animals were employed to further examine the role of menhaden oil in acute cutaneous responses to UV, i.e., erythema, edema, and ornithine decarboxylase (ODC) induction. After a 2‐week feeding period UV‐induced ODC activity in mice receiving 12 or 20% menhaden oil was 3 to 13‐fold lower than that of corn oil fed animals. Further studies showed that edema was also markedly decreased. Animals receiving menhaden oil required twice the level of irradiance to evoke a comparable erythema as that which occurred in corn oil fed animals.Menhaden oil exerted significant influence upon carcinogenic expression, as manifested in significantly longer tumor latent periods and lower tumor multiplicities when compared to corn oil fed animals. Although the mechanism(s) of these menhaden oil effects remains unknown, it is clear that this unique lipid has a pronounced influence upon cutaneous photoresponses. 15th Annual Meeting of the American Society for Photobiology, Bal Harbor, FL, June, 1987.

Inhibition of ornithine decarboxylase activity by small doses of α-difluoromethylornithine

The induction of ornithine decarboxylase (ODC) appears to be an important aspect of carcinogenesis. Agents which inhibit ODC have been shown to preclude cancer formation in many organ systems. We studied the dose and dose schedule of α-difluoromethylornithine (DFMO), a suicide inhibitor of ODC, needed to effectively inhibit ODC activity in mice. Our data demonstrate that doses many-fold lower than comparable maximal tolerated doses in humans can inhibit ODC activity in mice. In addition, a simplified, once daily dosage of DFMO appears adequate.

Effect of chloroform on hepatic and renal DNA synthesis and ornithine decarboxylase activity in mice and rats

Chloroform administered intraperitoneally (i.p.) to male mice and rats resulted in a dose-dependent increase in hepatic ornithine decarboxylase (ODC) activity. Maximal induction of the enzyme in mice was 10-fold and occurred at 375 mg/kg chloroform; in rats it was 52-fold and occurred at 750 mg/kg chloroform. Chloroform increased in mice and decreased in rats the rate of hepatic and renal DNA synthesis. Therefore, the induction of ODC activity in rat liver was not followed with an increase in DNA synthesis. The implications of these results to the proposed nongenetic mechanism of chloroform induction of hepatocellular carcinoma in mice and renal tumors in rats are discussed.

Effect of dehydration and arginine vasopressin on renal ornithine decarboxylase activity in mice

Dehydration of mice for 60 h caused a fall in the activity of renal ornithine decarboxylase. Administration of arginine vasopressin acutely produced a sharp increase in ornithine decarboxylase of the kidney 4 h later, while chronic intraperitoneal injection of vasopressin lowered renal enzyme activity in a manner analogous to that of dehydration. This bimodal response of the kidney to trophic hormonal stimulation appears to be different from that of other endocrine responsive organs.