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Tumor promoting phorbol ester derivatives increase ornithine decarboxylase ec 4.1.1.17 activity and poly amine biosynthesis in the liver of the rat and mouse


, : Tumor promoting phorbol ester derivatives increase ornithine decarboxylase ec 4.1.1.17 activity and poly amine biosynthesis in the liver of the rat and mouse. Carcinogenesis (Oxford) 3(7): 751-756

The ability of the phorbol-ester tumor promoters to alter ornithine decarboxylase (ODC) activity in the liver of the rat and mouse was determined. The injection of 12-O-tetradecanoyl phorbol-13-acetate (TPA, 100 .mu.g, i.p.) led to a 250-fold increase in hepatic ODC activity within 4 h of administration. This increase in ODC activity required both RNA and protein synthesis and did not occur when a variety of the non-tumor promoting phorbol-ester derivatives were administered to the rat. A distinct dose-dependent increase in hepatic ODC activity could be observed at 4 h following the injection of increasing amounts of TPA (0-100 .mu.g, i.p.). As little as 1.0 .mu.g TPA (i.p.) administered to a rat resulted in a significant stimulation in the activity of ODC in the liver compared to the control unstimulated values. Both 200 .mu.g and 500 .mu.g TPA produced less of an elevation in hepatic ODC activity than did the optimal dose of 100 .mu.g. In the mouse, the administration of 1 .mu.g and 20 .mu.g of TPA (i.p.) both led to a marked increase in hepatic ODC activity at 7 h and 4 h, respectively, following injection. A 4- to 5-fold increase in putrescine levels occurred in the rat liver in a biphasic manner between 4-8 h and 16-24 h following the injection of TPA (100 .mu.g). No alterations in either spermidine or spermine were observed during this period. The administration of 100 .mu.g of TPA to the rat did not alter the incorporation of [3H]thymidine into DNA in the liver compared to untreated control animals. Under these identical conditions partial hepatectomy led to a large increase in DNA synthesis.


Accession: 006847397

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Related references

Byus, C.V.; Weiner, R.A., 1982: Tumor promoting phorbol-ester derivatives increase ornithine decarboxylase activity and polyamine biosynthesis in the liver of the rat and mouse. The ability of the phorbol-ester tumor promoters to alter ornithine decarboxylase (ODC) activity in the liver of the rat and mouse was determined. The injection of 12-O-tetra-decanoyl phorbol-13-acetate (TPA, 100 microgram, i.p.) led to a 250-fold...

Takigawa, M.; Verma, A.K.; Simsiman, R.C.; Boutwell, R.K., 1982: Poly amine biosynthesis and skin tumor promotion inhibition of 12 o tetradecanoyl phorbol 13 acetate promoted mouse skin tumor formation by the irreversible inhibitor of ornithine decarboxylase ec 4.1.1.17 alpha di fluoromethyl ornithine. Application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse skin leads to the induction of ornithine decarboxylase (EC 4.1.1.17) and the accumulation of putrescine. The relevance of these TPA-induced changes to the mechanism of tumor promot...

Kido, H.; Fukusen, N.; Katunuma, N., 1987: Tumor-promoting phorbol ester amplifies the inductions of tyrosine aminotransferase and ornithine decarboxylase by glucocorticoid. In adrenalectomized rats, the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) markedly enhanced the inductions of tyrosine aminotransferase (TAT) and ornithine decarboxylase by glucocorticoids, even with sufficient concent...

Wu, V.S.; Byus, C.V., 1981: The induction of ornithine decarboxylase ec 4.1.1.37 by tumor promoting phorbol ester analogs in reuber h 35 hepatoma cells. The induction of ornithine decarboxylase (ODC) activity was studied in a rat hepatoma cell line (Reuber H35) incubated with a group of structurally-related phorbol ester analogs. A single application of 1.6 .mu.M of tumor promoter 12-O-tetradecano...

Wu, V.S.; Byus, C.V., 1981: The induction of ornithine decarboxylase by tumor promoting phorbol ester analogues in Reuber H35 hepatoma cells. Life Sciences 29(18): 1855-1863

Verma, A.K.; Boutwell, R.K., 1981: Characterization of arginase activity from mouse epidermis and its relation to ornithine decarboxylase ec 4.1.1.17 induction by the tumor promoting agent 12 o tetradecanoyl phorbol 13 acetate. Arginase, which catalyzes the cleavage of L-arginine to urea and ornithine, was detected in both soluble and particulate fractions of mouse epidermis. In a typical experiment, about 75 and 25% of the total arginase activity were associated with th...

Prakash, N.J.; Schechter, P.J.; Mamont, P.S.; Grove, J.; Koch-Weser, J.; Sjoerdsma, A., 1980: Inhibition of emt 6 tumor growth by interference with poly amine biosynthesis effects of alpha di fluoromethyl ornithine an irreversible inhibitor of ornithine decarboxylase ec 4.1.1.17. .alpha.-Difluoromethylorinithine (.alpha.-DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase (ODC, EC 4.1.1.17), retarded the growth rate of murine mammary EMT6 sarcoma in tissue culture. When female BALB/c mice were inoc...

Kohno T.; Mizuno N.; Tanii T.; Hamada T.; Yoshida H.; Otani S.; Matsui Yuasa I.; Morisawa S.; Nishizawa Y.; Morii H., 1989: Effects of 1 25 dihydroxyvitamin d 3 and fluorinated analog on the ornithine decarboxylase activity and its gene expression in mouse skin induced by phorbol ester tumor promoter. Clinical Research 37(2): 629A

Fujiki, H.; Mori, M.; Sugimura, T.; Hirota, M.; Ohigashi, H.; Koshimizu, K., 1980: Relationship between ornithine decarboxylase-inducing activity and configuration at C-4 in phorbol ester derivatives. Measurements were made of induction of ornithine decarboxylase activity after painting mouse skin with 12-O-hexadecanoyl-16-hydroxyphorbol-13-acetate and its two epimeric 4-deoxy-analogs, 12-O-hexadecanoyl-4-deoxy-16-hydroxyphorbol-13-acetate and...

Weeks, C.E.; Herrmann, A.L.; Nelson, F.R.; Slaga, T.J., 1982: Alpha di fluoromethyl ornithine an irreversible inhibitor of ornithine decarboxylase ec 4.1.1.17 inhibits tumor promoter induced poly amine accumulation and carcinogenesis in mouse skin. The role of ornithine decarboxylase (OrnDCase) and of the polyamines [putrescine (Put), spermidine (Spd), and spermine (Spm)] in mouse skin tumor promotion was investigated by the use of .alpha.-difluoromethylornithine (CHF2-Orn), an enzyme-activa...