Journal ArticleDOI
Suppression of tumor promoter phorbolmyristate acetate-induced chromosome breakage by antioxidants and inhibitors of arachidonic acid metabolism.
TLDR
It is concluded that the oxidative metabolism of arachidonic acid is involved in the induction of chromosomal aberrations by PMA in human lymphocytes and the step(s) in the arachIDonic acid cascade responsible for PMA clastogenicity is not yet identified.Abstract:
To gain insight into the mechanism of formation of chromosomal aberrations by the tumor promoter phorbolmyristate acetate (PMA) in human lymphocytes, we investigated the effect of antioxidants and inhibitors of arachidonic acid metabolism. Among the antioxidants bovine erythrocyte CuZn superoxide dismutase, glutathione peroxidase, mannitol (a scavenger of hydroxyl radicals), butylated hydroxytoluene and butylated hydroxyanisole were anticlastogenic while catalase and dimethylfuran (a scavenger of singlet oxygen) were inactive. These results show that the induction of aberrations by PMA occurs via indirect action, i.e. the intermediacy of superoxide and hydroxyl radicals. The following inhibitors of arachidonic acid metabolism were strongly anticlastogenic: the cyclo-oxygenase inhibitors indomethacin and flufenamic acid and the lipoxygenase inhibitor BN1015. Imidazole, nordihydroguaiaretic acid BN 1048 and 5,8,11,14-eicosatetraynoic acid were moderately active. The inhibitor of phospholipase A 2 , fluocinolone acetonide, was also anticlastogenic. We conclude that the oxidative metabolism of arachidonic acid is involved in the induction of chromosomal aberrations by PMA in human lymphocytes. However, because of the limited selectivity of these drugs, it is not yet possible to identify unambiguously the step(s) in the arachidonic acid cascade responsible for PMA clastogenicity.read more
Citations
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The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation.
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Dietary carcinogens and anticarcinogens Oxygen radicals and degenerative diseases
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Free radicals, antioxidant enzymes, and carcinogenesis
TL;DR: Free radicals are found to be involved in both initiation and promotion of multistage carcinogenesis, and antioxidants, the free radical scavengers, are shown to be anticarcinogens.
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Chromosome aberrations and sister chromatid exchanges in chinese hamster ovary cells: Evaluations of 108 chemicals
Sheila M. Galloway,M. J. Armstrong,C. Reuben,S. Colman,B. M. Brown,C. Cannon,A. D. Bloom,F. Nakamura,M. Ahmed,S. Duk,J. Rimpo,Barry H. Margolin,Michael A. Resnick,Beth Anderson,Errol Zeiger +14 more
TL;DR: Results from the testing of 108 coded chemicals in Chinese hamster ovary cells for the induction of chromosome aberrations and sister chromatid exchanges (SCEs) are presented.
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Drug-target interaction prediction from chemical, genomic and pharmacological data in an integrated framework
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References
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Journal ArticleDOI
Superoxide radical inhibits catalase.
Y Kono,Irwin Fridovich +1 more
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Journal ArticleDOI
Identification of 4-hydroxynonenal as a cytotoxic product originating from the peroxidation of liver microsomal lipids☆
TL;DR: Investigations suggest that as compared to 4-hydroxynonenal very low amounts of other 4-Hydroxyalkenals are formed by actively peroxidizing liver microsomes, and this finding may help to elucidate the mechanism by which lipid peroxidation causes deleterious effects on cells and cell constituents.
Journal Article
Inhibition by prostaglandin synthesis inhibitors of the induction of epidermal ornithine decarboxylase activity, the accumulation of prostaglandins, and tumor promotion caused by 12-O-tetradecanoylphorbol-13-acetate.
TL;DR: The findings that the application of indomethacin prior to TPA treatment inhibits the accumulation of prostaglandins, the induction of ODC activity, and the formation of skin papillomas suggest that TPA-induced O DC activity may be an important component of the mechanism of skin tumor promotion.
Journal ArticleDOI
DNA strand breakage in human leukocytes exposed to a tumor promoter, phorbol myristate acetate
TL;DR: The phorbol myristate acetate-stimulated respiratory burst in human peripheral blood leukocytes is associated with extensive DNA strand breakage as mentioned in this paper, which occurs before gross cellular damage.
Journal ArticleDOI
Tumour promoter phorbol-12-myristate-13-acetate induces chromosomal damage via indirect action.
Ingrid Emerit,Peter Cerutti +1 more
TL;DR: It is reported here that PMA, but not its weakly or non-promoting derivatives, induced chromosomal aberrations with high efficiency in phytohaemagglutinin (PHA)-stimulated human lymphocytes, but was only a weak producer of SCE.
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Tumour promoter phorbol-12-myristate-13-acetate induces chromosomal damage via indirect action.
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