calcimycin and Hyperplasia

To investigate whether empagliflozin could prevent injury-induced vascular neointimal hyperplasia and to further explore its mechanism.. Male C57BL/6J mice were divided into two groups with or without the empagliflozin treatment, and carotid ligation injury was performed to induce neointimal hyperplasia. The injured carotid arteries were collected for Western blotting (WB), histology and immunofluorescence analysis after four weeks. The inflammatory responses were analyzed by qRT-PCR to detect the inflammatory gene mRNA expression. To further explore its mechanism, HUVECs were treated with TGFβ-1 to induce EndMT followed by empagliflozin or vehicle treatment in vitro. A23187 (Calcimycin), an agonist of NF-κB signaling was used in the experiment.. The wall thickness and the neointima area was significantly reduced in the empagliflozin treatment group on day 28 after artery ligation. The Ki-67 positive cells were 28.33 ± 12.66% and 48.83 ± 10.41% in the empagliflozin-treated group and control group, respectively (P < 0.05). The mRNA expression levels of the inflammatory genes and inflammatory cells were decreased in the empagliflozin treatment group, as well as the MMP2 and MMP9. Meanwhile, empagliflozin can significantly reduce the migratory ability of inflammatory-treated HUVECs. The CD31 was increased in the TGFβ1+empagliflozin group, whereas the FSP-1, phosphorylation of TAK-1 (p-TAK-1) and phosphorylation of NF-κB (p- NF-κB) expression level were decreased, compared to the control group without empagliflozin treatment. However, the expression level of FSP-1 and p-NF-κB were reversed after co-treatment with A23187, whereas the p-TAK-1 expression level was without any significant difference.. Empagliflozin inhibits the inflammation-induced EndMT via the TAK-1/NF-κB signaling pathway.

Topics: Animals; Calcimycin; Hyperplasia; Male; Mice; Mice, Inbred C57BL; Neointima; NF-kappa B; RNA, Messenger; Vascular System Injuries

Cynanchum atratum Bunge (Apocynaceae) is a folk medicine to treat skin inflammatory diseases. However, the effects of C. atratum on atopic dermatitis have not been elucidated. In this study, we evaluate the effects of aqueous extract of C. atratum (CA) and its molecular mechanism on atopic dermatitis (AD). 1 and 100mg/mL CA were topically applied to 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions for 11 days. The number of scratching behavior was evaluated for 20min. AD-like symptoms including elevated serum IgE, skin hyperplasia and mast cell infiltration were investigated. The expressions of pro-inflammatory cytokines and mediators were analyzed in AD-like skin legions. In addition, pro-inflammatory cytokine production was confirmed in human mast cells (HMC)-1 stimulated with PMA plus A23187 (PMACI). Topical application of CA attenuated total serum IgE level and scratching behavior. Skin hyperplasia including epidermis and dermis was ameliorated in CA-treated skin legions. The number of infiltrated mast cells was significantly decreased by CA treatment. In addition, CA reduced pro-inflammatory cytokines, such as IL-6, IL-1β and TNF-α and Th2 cytokine, IL-4, in both of AD-like skin lesions and PMACI-sensitized HMC-1 cells. Furthermore, CA decreased the expressions of NF-κB, phospho-IκBα and MAP kinase. These results suggest the inhibitory effects of CA on the development of AD by regulating pro-inflammatory cytokines and mediators. CA could be an effective substance for the treatment of AD.

Topics: Animals; Calcimycin; Cytokines; Dermatitis, Atopic; Dermis; Dinitrochlorobenzene; Epidermis; Female; Hyperplasia; Immunoglobulin E; Inflammation; Interleukin-6; Mast Cells; Mice; Mice, Inbred BALB C; NF-kappa B; NF-KappaB Inhibitor alpha; Plant Extracts; Tumor Necrosis Factor-alpha; Vincetoxicum

Hyperlipidemia may increase endothelial damage and promote accelerated atherogenesis in graft coronary vasculopathy. To study the effects of hypercholesterolemia on coronary endothelial dysfunction, intimal hyperplasia, and lipid content, a porcine model of heterotopic heart transplantation, allowing nonacute rejection without immunosuppressive drugs, was used. A high cholesterol diet was fed to donor and recipient swine 1 month before and after transplantation. The endothelial function of coronary arteries of native and transplanted hearts from cholesterol-fed animals was studied in organ chambers 30 days after implantation and compared with endothelial function in arteries from animals fed a normal diet. The total serum cholesterol increased 3-fold in donors and recipients. Endothelium-dependent relaxations to serotonin, to the alpha(2)-adrenergic agonist UK14,304, and to the direct G-protein activator sodium fluoride were decreased significantly in allografted hearts compared with native hearts from both groups. Relaxations to the calcium ionophore A23187 and bradykinin were decreased significantly in allografts from animals fed the high cholesterol diet. The prevalence of intimal hyperplasia was significantly increased in coronary arteries from hypercholesterolemic swine. There was a significant increase in the lipid content of allograft arteries of hypercholesterolemic recipients. Hypercholesterolemia causes a general coronary endothelial dysfunction, increases the prevalence of intimal hyperplasia, and augments the incorporation of lipids in the vascular wall after heart transplantation. Hyperlipidemia accelerates graft coronary atherosclerosis through its effects on the endothelium.

Topics: Adrenergic alpha-Agonists; Animals; Arteriosclerosis; Biological Transport; Brimonidine Tartrate; Calcimycin; Calcium; Cholesterol, HDL; Cholesterol, LDL; Coronary Vessels; Diet, Atherogenic; Dinoprost; Dose-Response Relationship, Drug; Endothelium, Vascular; Erythrocyte Count; Female; Free Radical Scavengers; Heart Transplantation; Hematocrit; Hemoglobins; Hypercholesterolemia; Hyperplasia; Ionophores; Male; Myocardium; Postoperative Period; Potassium Chloride; Quinoxalines; Serotonin; Swine; Transplantation, Homologous; Tunica Intima; Vasodilation

Bladder outlet obstruction (BOO) is a common disorder that is associated with altered bladder structure and function. For example, it is well established that BOO results in hypertrophy and hyperplasia of the bladder smooth muscle as well as detrusor instability. Since prostaglandins (PGs) and cyclic nucleotides (cyclic AMP [cAMP] and cyclic GMP [cGMP]) mediate both smooth muscle tone and proliferation, it is reasonable to suggest that changes in their levels may be involved in the pathophysiology of BOO-associated bladder disorders. Hence, the objective of this study was to investigate cyclic AMP, cyclic GMP and prostaglandins in the bladder of a rabbit model of BOO. BOO was induced in adult male New Zealand White rabbits. After 3 weeks, urinary bladders were excised, weighed and cut into segments. They were then incubated with stimulators of PGs, cAMP and cGMP and the formation of PGs, cAMP and cGMP were measured using radioimmunoassays. There was a significant increase in the obstructed bladder weights (P=0.002). The formation of PGE2, PGI2, cAMP and cGMP was significantly diminished in the detrusor (P<0.05) and bladder neck (P<0.05) in the BOO bladders compared to age-matched controls. Since PGE2, PGI2, cAMP and cGMP are known to inhibit the proliferation of smooth muscle cells (SMCs), the decreased synthesis of these factors, in BOO, may play a role in bladder SMC hypertrophy/hyperplasia. Our study points to the possible use of drugs that modulate the NO-cGMP and/or PG-cAMP axes in BOO-associated bladder pathology.

Topics: Acetylcholine; Animals; Calcimycin; Cyclic AMP; Cyclic GMP; Dinoprostone; Disease Models, Animal; Epoprostenol; Hyperplasia; Hypertrophy; In Vitro Techniques; Male; Muscle, Smooth; Organ Size; Phorbol 12,13-Dibutyrate; Prostaglandins; Rabbits; Urinary Bladder; Urinary Bladder Neck Obstruction

Recent evidence suggests that vascular endothelial growth factor (VEGF), in addition to stimulating angiogenesis, also serves a repair/maintenance or survival function, modulating various aspects of endothelial cell function. This study was designed to examine the effect of VEGF pretreatment in a model of vein graft intimal hyperplasia.. Reversed jugular vein-to-common carotid artery interposition grafts were constructed in New Zealand White rabbits. White rabbits. Vein conduits were immersed in solution containing 500 micrograms rhVEGF165 or saline solution for 20 minutes before implantation. Twenty-eight days later the vein grafts and contralateral control jugular veins were harvested for either histologic or isometric tension studies.. VEGF-treated vein grafts showed a 23% reduction in intimal area (0.76 +/- 0.07 mm2 vs 0.98 +/- 0.06 mm2; p = 0.028) and a 30% reduction in intimal thickness (62 +/- 6 microns vs 89 +/- 5 microns; p = 0.001) when compared with control grafts. After precontraction with norepinephrine, the maximal relaxation to acetylcholine (endothelium-dependent, receptor-mediated agonist) for control vein grafts was 0%, whereas for VEGF-treated vein grafts it was 25% +/- 9% (p < 0.05 vs control grafts). The maximal relaxation to the calcium ionophore A23187 (endothelium-dependent, receptor-independent agonist) was also greater in VEGF-treated grafts than in control grafts (172.3% +/- 19.4% vs 122.5% +/- 13.7%; p < 0.05). There was no difference in the response to sodium nitroprusside (endothelium-independent agonist) between the two groups.. A single topical application of VEGF before implantation reduces intimal hyperplasia and improves endothelial function in a rabbit vein graft model. Further evaluation of this simple strategy to improve vein graft patency appears warranted.

Topics: Acetylcholine; Animals; Calcimycin; Endothelial Growth Factors; Endothelium, Vascular; Hyperplasia; Lymphokines; Male; Nitroprusside; Rabbits; Tunica Intima; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Vasodilation; Veins

Peritoneal mast cell hyperplasia was investigated in rats after evoking IgE antibody-antigen reaction. Rats were immunized with antigen and then passively sensitized with monoclonal IgE antibody before antigen challenge. A significant increase in the number of peritoneal mast cells was observed 3 weeks after the antigen challenge in the peritoneal cavity, although the histamine content of the mast cells was decreased significantly. In rats without prior immunization, these changes were not observed. Stimulation with compound 48/80 or calcium ionophore A23187 did not affect the number of mast cells. This model may prove to be a useful tool for studying the mechanisms of mast cell hyperplasia and recruitment of mast cell precursors in vivo.

Topics: Animals; Antigens; Ascaris suum; Calcimycin; Cell Count; Dinitrophenols; Histamine; Hyperplasia; Immunization; Immunoglobulin E; Male; Mast Cells; p-Methoxy-N-methylphenethylamine; Peritoneal Cavity; Rats; Rats, Wistar

Experiments were designed to determine the effects of blood flow on endothelium-dependent relaxations in canine vein grafts.. Blood flow through reversed femoral vein grafts was either increased by a distal arteriovenous fistula (increased flow), unmanipulated (normal flow), or reduced by a proximal adjustable clamp (reduced flow). Six weeks after implantation, blood flow through the graft was measured. Rings cut from grafts were suspended for the measurement of isometric force in organ chambers to determine endothelial function.. Blood flow was significantly greater in grafts with a distal fistula compared to grafts with normal or decreased flow. Endothelium-dependent relaxations to acetylcholine were absent in all grafts. Endothelium-dependent relaxations to adenosine diphosphate, thrombin, and the calcium ionophore A23187 were less in grafts with reduced flow compared with grafts with increased flow. Relaxations to these agents in grafts with increased flow were reduced by an analog of L-arginine. Neointimal hyperplasia was increased in grafts with reduced flow.. These data demonstrate that chronic diminution of blood flow decreases receptor-mediated release of endothelium-derived relaxing factors and increases neointimal hyperplasia in canine vein grafts. The production of endothelium-derived relaxing factors, one of which is nitric oxide, may influence the development of myointimal hyperplasia in vein grafts.

Topics: Acetylcholine; Adenosine Diphosphate; Adrenergic alpha-Agonists; Animals; Arginine; Arteriovenous Shunt, Surgical; Blood Flow Velocity; Brimonidine Tartrate; Calcimycin; Constriction; Dinoprost; Dogs; Endothelins; Endothelium, Vascular; Femoral Artery; Femoral Vein; Hyperplasia; Male; Models, Biological; Neovascularization, Pathologic; Nitric Oxide; omega-N-Methylarginine; Quinoxalines; Thrombin; Tunica Intima; Vascular Patency

The effects of promoter treatments prior to initiation on subsequent promotion by mezerein were examined in SENCAR mice. Groups of mice received two applications of various complete as well as first and second stage promoters given at various time intervals prior to initiation ranging from 3 days to 10 weeks. The mice were then initiated with 2 micrograms of 7,12-dimethylbenz[a]anthracene (DMBA) followed 2 weeks later by twice-weekly treatments with 2 micrograms of mezerein. The papilloma response in mice, receiving pretreatments with 2 micrograms of 12-O-tetradecanoylphorbol-13-acetate (TPA) either 3 days, 1, 2, 3 or 5 weeks before initiation, was similar to that seen when TPA was given after initiation during stage I of promotion followed by stage II of promotion with mezerein (4-5 papillomas per mouse in all groups). Surprisingly, pretreatment with the stage II promoter, mezerein (2 micrograms), either 2 or 5 weeks prior to initiation, also gave papilloma responses similar to that induced with the standard two-stage promotion protocol (4.7 and 6.4 papillomas per mouse, respectively). The papilloma response was less than that in the standard two-stage promotion protocol when pretreatments with the stage I promoter A23187 (80 micrograms/mouse) were given either 2 or 5 weeks before initiation (2.6 and 2.3 papillomas per mouse, respectively). However, a repeat experiment (currently in progress) with a higher dose of A23187 (160 micrograms/mouse) given 2 weeks prior to initiation indicates that it is more effective than the 80 micrograms dose. When the time interval between pretreatment and initiation was increased to 10 weeks, the papilloma response with TPA and A23187 pretreatment was reduced to below two papillomas per mouse and with mezerein pretreatment to below three papillomas per mouse, indicating the effect was reversible. Histological changes in epidermis of mice which received two applications of these compounds correlated with the tumor response. In this regard, treatment with two applications of TPA and mezerein resulted in an epidermal hyperplasia of similar magnitude (epidermal thickness of 53.5 +/- 1.5 and 50.0 +/- 1.1 microns, respectively). The hyperplasia produced by treatment with two applications of 80 micrograms A23187 (39.4 +/- 1.8 microns) was significantly less. The ability of pretreatments with benzoyl peroxide (20 mg) and chrysarobin (50 micrograms) to affect the subsequent promoting activity of mezerein was also examined.(ABSTRAC

Topics: Animals; Calcimycin; Diterpenes; Drug Synergism; Female; Hyperplasia; Mice; Papilloma; Skin; Skin Neoplasms; Terpenes; Tetradecanoylphorbol Acetate

Cheek pouches of male Syrian golden hamsters were topically treated with a single dose of TPA (.5 microgram), calcium ionophore A23187 (75 micrograms) or Sn-1,2-dioctanoylglycerol (DiC8) (500 micrograms) dissolved in 0.25 ml acetone. Acetone-treated animals served as controls. After 48 h the mitotic index for the control group was 1.1 +/- 0.1 per 1 mm of the basement membrane length. All the test congeners exhibited higher mitotic indices than controls: TPA (4.8 +/- 0.4), A23187 (3.9 +/- 0.3), DiC8 (2.1 +/- 0.2). All groups exhibited an increase in the epithelial thickness manifested by cellular hyperplasia. The treatment of the pouches with the anti-inflammatory agent fluocinolone acetonide inhibited the mitogenic and hyperplasiogenic affects on the epithelium induced by the various test chemicals. These studies indicate a possible role of calcium-phospholipid dependent protein kinase (protein kinase C) in the mediation of oral epithelial cell proliferation.

Topics: Animals; Calcimycin; Cell Division; Cheek; Connective Tissue; Connective Tissue Cells; Cricetinae; Diglycerides; Epithelial Cells; Epithelium; Fluocinolone Acetonide; Glycerides; Hyperplasia; Male; Mesocricetus; Mitosis; Mouth Mucosa; Tetradecanoylphorbol Acetate

We have studied the effects of the potent tumour promoter phorbol, 12-myristate, 13-acetate (PMA) and two non-promoting hyperplasiogenic compounds ethyl phenylpropriolate (EPP) and the divalent cation ionophore A23187 on the terminal differentiation of normal and transformed human keratinocytes using the loss of cloning efficiency and the formation of cornified envelopes as markers of the differentiated state. PMA induced terminal differentiation in a far greater proportion of normal keratinocytes than it did in the squamous cell carcinoma line SCC-27 but EPP and the calcium ionophores A23187 and Br-X537A had no such differential effect, possibly explaining the poor promoting ability of the last three compounds.

Topics: Alkynes; Calcimycin; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line; Cell Transformation, Neoplastic; Cells, Cultured; Clone Cells; Humans; Hyperplasia; Keratins; Phorbols; Skin; Tetradecanoylphorbol Acetate

The transmembrane potential of HEL30 keratinocytes and 3T3 fibroblasts has been determined by measuring the distribution of labelled triphenylmethylphosphonium bromide. The tumor-promotor 12-O-tetradecanoylphorbol 13-acetate (1-5 microM) induces hyperpolarization in 3T3 cells but does not exert any effect on the membrane potential of keratinocytes, whereas the divalent cation ionophore A23187 (0.5 - 1 microM) hyperpolarizes keratinocytes and probably also 3T3 cells. Studies on Na+ and Rb+ fluxes, as well as with different inhibitors, indicate that the hyperpolarizing effect is the consequence of an increased Na+ influx which in turn stimulates the Na+/K+-dependent ATPase. No causal relationship seems to exist between the change of the membrane potential and arachidonic acid release (and subsequent prostaglandin synthesis) which is induced by both drugs in both cell lines. Since the induction of the arachidonic cascade (by both agents) as well as the stimulation of Na+ influx (by A23187) are found to be critically dependent on extracellular Ca2+ and are inhibited by 'Ca2+-blockers', it is concluded that both reactions are triggered by the same event (Ca2+ translocation) but proceed independently of each other. The release of arachidonic acid is already stimulated under conditions where a measurable influx of Ca2+ is not yet observed. This indicates a local mobilization of Ca2+, perhaps across the plasma membrane. It is concluded that monovalent cation fluxes and changes of the membrane potential are not critically involved in the stimulation of the arachidonic acid cascade and cellular proliferation by agents which induce epidermal hyperplasia in vivo.

Topics: Animals; Arachidonic Acids; Biological Transport; Calcimycin; Cations, Divalent; Cell Division; Cell Line; Epidermis; Fibroblasts; Hyperplasia; Membrane Potentials; Mice; Mitogens; Phorbols; Tetradecanoylphorbol Acetate

Long-term treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) of dorsal skin of 7,12-dimethylbenz(a)anthracene-initiated Syrian golden hamsters does not lead to the formation of epithelial tumors and leaves the epidermis essentially unchanged. However, previous histological studies by others have shown that hamster epidermis can be hyperplastically transformed by a single application of TPA but that the tissue is capable of gradually adapting to the drug after extended TPA exposure. We have investigated the response of hamster back epidermis to single and multiple treatments with increasing doses of TPA with regard to histological, proliferative, and biochemical alterations, and we show that in our animal strain the dorsal epidermis is resistant to even a single exposure to TPA, although the clearance rate of TPA is comparable to that in mouse epidermis and the metabolism of the substance is negligible. In contrast, the epidermis could be moderately stimulated by a single application of the nonpromoting calcium ionophore A 23187 and exhibited a strong proliferate and hyperplastic response following the simultaneous exposure to the calcium ionophore and TPA. Both types of hyperproliferation did not reveal an initial depression of the proliferative activity and were accompanied by typical alterations of the keratin polypeptide pattern, which was not detectable after treatment with TPA alone.

Topics: Adaptation, Physiological; Administration, Topical; Animals; Anti-Bacterial Agents; Calcimycin; Cell Division; Cricetinae; Drug Resistance; Hyperplasia; Keratins; Male; Mesocricetus; Phorbols; Skin; Tetradecanoylphorbol Acetate; Time Factors

Topics: Alkynes; Anthralin; Calcimycin; Carcinogens; Diterpenes; Epidermal Cells; Epidermis; Hyperplasia; Keratins; Phorbol Esters; Terpenes; Tetradecanoylphorbol Acetate

Ca, Mg (0.1 or 0.2M) and ionophore A23187 (10(-5) - 10(-4)M) promoted benign hyperplastic lesions (BHLs) to a highly variable degree when applied topically in hamster cheek pouch after initiation with 7, 12-dimethylbenz(a)anthracene (DMBA). The changes in the promoting effects of Ca and Mg between experiments were not parallel. Mg but not Ca inhibited retinyl acetate-induced progression of BHLs to advanced tumors. Cyclic adenosine 3',5'-monophosphate (cAMP) (10(-5) - 10(-3)M) promoted BHLs. The results are discussed in terms of possible mechanisms involved.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Calcimycin; Calcium; Cheek; Cricetinae; Cyclic AMP; Female; Hyperplasia; Magnesium; Mesocricetus; Mouth Mucosa; Neoplasms, Experimental

Topics: Calcimycin; Cell Division; Cocarcinogenesis; Dinoprost; Dinoprostone; Epidermal Cells; Hyperplasia; Indomethacin; Prostaglandins E; Prostaglandins F; Skin; Skin Neoplasms; Structure-Activity Relationship; Tetradecanoylphorbol Acetate

The percentages of dark keratinocytes was quantitatively assessed in normal epidermis of Sencar mice before and after birth and in adult epidermis after topical application of several compounds of varying promoting efficiency. The percentage of dark keratinocytes reached a maximum at the 19th day of gestation (approximately 40%) and fell abruptly after birth (approximately 3%). Old animals exhibited a very low number of dark basal cells (0.2%). After topical application of the weak promoters resiniferotoxin, anthralin, ethylphenylpropiolate, and 12-deoxyphorbol-13-2,4,6-decatrienoate, the percentage of dark cells in young adult epidermis did not differ markedly from that in control (acetone-treated) specimens. The strong first-stage promoters 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate and calcium ionophore A 23187, as well as the strong complete promoter 12-deoxyphorbol-13-deoxyphorbol-13-decanoate, induced the appearance of large numbers of dark keratinocytes, in a percentage similar to that seen after 12-O-tetradecanoylphorbol-13-acetate application (approximately 20%). The similarities between the dark keratinocytes seen after topical application of 12-O-tetradecanoylphorbol-13-acetate or other strong promoters and the dark cells observed in the fetal epidermis before the onset of the adult type of epidermal keratinization indicate that potent and/or first stage tumor promoters can be identified by their ability to induce cells resembling fetal-type dedifferentiated keratinocytes.

Topics: Administration, Topical; Age Factors; Alkynes; Animals; Anthralin; Calcimycin; Carcinogens; Epidermis; Female; Gestational Age; Hyperplasia; Methods; Mice; Phorbol Esters; Thymidine

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.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Animals; Calcimycin; Dose-Response Relationship, Drug; Epidermis; Female; Hyperplasia; Mice; Mitosis; Neoplasms; Phorbol Esters; Phorbols; Skin; Structure-Activity Relationship

Ca ion, ionophore 23187 and the membrane labilizing agents triton X-100, trypsin and phospholipase C promoted benign hyperplastic lesions (BHLs) but only rarely advanced tumors in hamster cheek pouch mucosa, which had been initiated with 7,12 dimethylbenz (a) anthracene. Retinyl acetate (RA) and croton oil markedly promoted both BHLs and advanced tumors. These results suggest that pathways modulated by intracellular Ca cause initiation-stabilized release from growth control, thus the promotion of BHLs, whereas additional mechanisms are required for the progression of BHLs to more advanced tumors. Some Ca-modulated systems which could be involved in promotion of BHLs are discussed in the light of published literature.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Calcimycin; Calcium; Cheek; Cricetinae; Female; Hyperplasia; Membranes; Mesocricetus; Neoplasms; Neoplasms, Experimental