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Biomedical subjects

F Marks

Publications and source records attributed to F Marks.

At least 199 records · Page 11Linked to original sources
PubMed1982

Effects of phorbol esters on basal epidermal cells derived from ear skin of adult guniea pigs.

In cultures of basal epidermal cells obtained from ear skin of adult guinea pigs, the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate induces cellular proliferation which is prostaglandin dependent and inhibited by indomethacin. Inhibition by indomethacin can be overcome by prostaglandins E2 and F2 alpha, with prostaglandin F2 alpha being more effective. The concomitant induction of ornithine decarboxylase activity is insensitive to indomethacin inhibition. The nonpromoting derivative 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate evokes a prostaglandin-independent, i.e., indomethacin-insensitive, stimulation of cell proliferation without inducing ornithine decarboxylase activity.

Animals↗
PubMed1982

Preparation of retinoic acid esters of phorbol derivatives.

The synthesis of 12-O-retinoylphorbol-13-acetate (RPA), an incomplete tumor promoter (second stage promoter) is described. The preparation starts with phorbol-13-acetate-20-tritylether which is acylated by a carbodiimide method to yield its 12-retinoate. The latter is detritylated by acidic methanol to give RPA. Following an analogous procedure, the 4-methyl-ether of RPA is prepared from 4-O-methylphorbol-13-acetate-20-tritylether.

Animals↗
PubMed1981

Agonist- and mitogen-induced desensitization of isoproterenol-stimulated cyclic AMP formation in mouse epidermis in vivo.

Injection of the beta-adrenergic agonist isoproterenol causes a rapid desensitization of cyclic AMP formation to subsequent beta-adrenergic challenge in mouse epidermis. Long-lasting catecholamine refractoriness is also observed after prolonged treatment of mouse skin with certain mitogens such as the phorbol ester TPA (tumor promoter), 12-retinoylphorbol-acetate, the TPA-analogue C14:4phorbol acetate or the divalent cation ionophore A 23187 but not after mitogenic stimulation by phorbol-12,13-dibenzoate and 4-O-methyl-TPA or by means of chemical depilation, removal of the horny layer or skin massage. Thus no clear-cut correlation exists between the desensitizing efficacy of a given treatment and its ability to provoke epidermal hyperplasia and to promote skin tumor formation. Both, agonist- and mitogen-induced desensitization are dependent on protein synthesis in epidermis, the mitogen-induced effect is in addition dependent on RNA synthesis. The putative desensitizing protein is not cyclic AMP phosphodiesterase but could be a feedback inhibitor of receptor-cyclase interaction ("refractoriness protein") which has recently been proposed to be responsible for catecholamine tachyphylaxis in certain in vitro systems. In contrast to epidermal hyperproliferation mitogen-induced tachyphylaxis is not mediated by prostaglandin synthesis and is apparently also independent of initial cyclic AMP formation. It can be prevented, however, by the antimitotic synthetic corticoid fluocinolone acetonide but not by colchicine, vincristine cytochalasin B or adrenergic blockers.

Adenylyl Cyclases↗
PubMed1981

Arachidonic acid and prostaglandin E2 release and enhanced cell proliferation induced by the phorbol ester TPA in a murine epidermal cell line.

Addition of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) to a murine epidermal cell line leads to an early induction of the arachidonic acid cascade as measured by the release of [14C]arachidonic acid and [14C]prostaglandin E2 into the medium, to an induction of the ornithine decarboxylase and finally to cell proliferation. The results show that TPA induces the same sequence of biochemical events in vitro as in mouse epidermis in vivo. Thus, the in vitro system seems to be suitable to study the role of early membrane effects and membrane lipid turnover in the induction of cell proliferation and hyperplasia by TPA.

Animals↗
PubMed1981

Histone phosphorylation in phorbol ester stimulated and beta-adrenergically stimulated mouse epidermis in vivo and characterization of an epidermal protein phosphorylation system.

Under certain physiological conditions a change in the phosphorylation of histones in mouse epidermis in vivo was observed. Thus a single local application of the tumor-promoting mitogen 12-O-tetradecanoylphorbol-13-acetate caused a long-lasting increase of histone H1 phosphorylation which paralleled stimulated cell proliferation. Injection of the antimitotic beta-adrenergic agonist isoproterenol led to a temporary decrease in the rate of phosphorylation of H1, H2A and H2B immediately after cyclic AMP accumulation. A complete protein phosphorylation system could be demonstrated in mouse epidermis homogenates. The following enzyme activities were partially purified and characterized: a cyclic AMP-dependent histone kinase; a 'casein kinase' and an 'unspecific' protein kinase; a histone-specific protein phosphatase; and two 'unspecific' phosphoprotein phosphatases. In addition, a stimulatory effect of cyclic GMP on histone phosphorylation was observed. The enzymes were found to be predominantly localized in the 105000 X g supernatant, but a small proportion of protein kinase and phosphatase activity could be regularly demonstrated in cell nuclei.

Animals↗
PubMed1981

Skin tumor promotion by phorbol esters is a two-stage process.

In the semisynthetic compound phorbol 12-retinoate 13-acetate (PRA), the antipromoting principle of vitamin A acid is combined with the structure of a phorbol ester tumor promoter. In skin of NMRI mice, a single topical application of PRA induces skin inflammation, epidermal proliferation, and sustained hyperplasia to a similar extent and apparently along the same pathway as an equimolar dose of the strong tumor promoter phorbol 12-myristate 13-acetate (PMA). The mitogenic effects of both PRA and PMA are mediated by prostaglandin E synthesis. However, in mouse skin initiated with 7,12-dimethylbenz[a]anthracene, PRA does not promote tumor development, even at a high dose. Under continuous PRA treatment, however, one to four applications of PMA (insufficient by itself to promote tumor growth) gave a strong tumor response. Thus, it can be demonstrated that the effects necessary for tumor promotion can be brought about by a single application of PMA and that the subsequent chronic hyperproliferation of epidermis is probably necessary only to make the tumors visible. By using the nonpromoting irritant mitogen PRA, the concept of two-stage tumor promotion can thus be strongly supported. Furthermore, in the NMRI mouse, PRA is a much more potent second-stage promoter than mezerein, recently reported to be an incomplete promoter in the Sencar mouse.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Prostaglandin E-mediated mitogenic stimulation of mouse epidermis in vivo by divalent cation ionophore A 23187 and by tumor promoter 12-O-tetradecanoylphorbol-13-acetate.

When applied to mouse skin in vivo, both the strong tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) (2 nmol) and the divalent cation ionophore A 23187 (200 nmol) caused the same responses, i.e., skin inflammation and prostaglandin E2-mediated epidermal hyperplasia. In both cases, these events were accompanied by certain biochemical reactions in the epidermis such as an increase in the biosynthesis of and sensitivity to prostaglandin E2, increase in ornithine decarboxylase and phosphodiesterase activities, and refractoriness of cyclic adenosine 3':5'-monophosphate production to beta-adrenergic stimulation. In contrast to A 23187, TPA did not induce degranulation of mast cells; whereas, in contrast with TPA, A 23187 did not show tumor-promoting activity. These results indicate that the observed biological effects of TPA are no indication of tumor-promoting ability and that, on the other hand, the mitogenic effects of A 23187 are possibly not due to its properties as a calcium ionophore.

Animals↗
PubMed1980

Effect of phorbol ester application and other mitogenic treatments on 3',5'-cyclic-nucleotide phosphodiesterase activity in mouse epidermis in vivo.

The effects of phorbol ester application and of other mitogenic treatments on the activity of 3',5'-cyclic-nucleotide phosphodiesterase were investigated in dorsal mouse epidermis in vivo. Local treatment with either the weak tumor promoter phorbol 12,13-dibenzoate or the strong promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) increased the activity of the high affinity enzyme (Km = 4 microM). The enzymic changes began within the first hour after application, and lasted for about 5 days. maximal stimulations of approximately 300--400% were reached after 3--6 h with TPA application, whereas with phorbol dibenzoate the maximum could only be reached after 1--2 days. TPA stimulation of the enzyme depended on doses within the range of 0.2 to 20 nmol and could be completely prevented by cycloheximide, but not by 5-azacytidine, actinomycin D, 5,8,11,14-eicosatetraynoic acid or indomethacin. No evidence could be found for cAMP participation in enzyme induction. An increase in enzyme activity could also be observed after other mitogenic treatments such as local application of the weakly promoting phorbol esters C14:4-phorbol acetate ("Ti8") and 4.O-methyl-TPA, or of the non-promoting divalent cation ionophore A 23187, as well as after treatment with a depilatory cream. Skin massage or removal of the horny layer, which also stimulate mitosis, did not evoke a significant increase in enzyme activity. No apparent correlation exists between the hyperplasiogenic and tumor-promoting effectiveness of a manipulation and its effect on epidermal 3',5'-cyclic-nucleotide phosphodiesterase.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1979

Appearance of growth-inhibiting activity (G1 chalone) during ontogenetic development of rat and chick epidermis in vivo and in vitro.

A comparative study was carried out between the stage of embryonic development of epidermis and its content of growth-inhibitory activity (G1 chalone). Injections of aqueous extracts from keratinized fetal rat or chick embryo epidermis led to a depression of DNA-synthesis in adult mouse epidermis, whereas extracts from undifferentiated epidermis did not contain such an activity.

Animals↗