Lowering of innate resistance of the lungs to the growth of blood-borne cancer cells in states of topical and systemic stress.
The survival and clonogenic growth (measured in terms of colony forming efficiency (CFE) of intravenously injected (i.v.) Walker (W256) tumour cells in the lungs of rats was greatly enhanced by states of topical and systemic stress induced by the intraperitoneal (i.p.) injection of rats with a single dose of 10(-5)-10(-3) mmol g-1 body weight of adrenaline and other beta-adrenergic agonists, inflammatory agents (including local x-irradiation), convulsive seizures, "tumbling" or physical restraint. Lowering of innate resistance of the host to growth of seeded tumour cells induced by states of topical and systemic stress, and by the addition of an excess of lethally irradiated (LI) tumour cells to i.v. injected intact tumour cells, were all potentiated by treatment of rats with aminophylline, an inhibitor of cyclic AMP phosphodiesterase. Enhancement of tumour growth by systemic stress was inhibited by bilateral total or medullary adrenalectomy and is attributed to the release and actions of endogenous adreno-medullary hormones. Alpha-adrenergic and most non-adrenergic agents administered in maximum tolerated doses did not significantly affect host resistance to tumour growth in the lungs. These findings, correlated with measurements of cyclic AMP in the lungs of normal and stressed rats, suggest that changes in the resistance of the host to tumour growth involve changes in cyclic nucleotide metabolism in the target tissues (tumour bed); possible mechanisms of action of cyclic nucleotides in this respect are discussed.
D000315:Adrenalectomy; D000628:Aminophylline / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D002279:Carcinoma 256, Walker / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007109:Immunity / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology*; D009360:Neoplastic Cells, Circulating; D010433:Pentylenetetrazole; D011830:Radiation Effects; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D013312:Stress, Physiological / Q000276:immunology*; D013565:Sympatholytics / Q000494:pharmacology
D007093:Imidazoles; D013565:Sympatholytics; D000628:Aminophylline; D012701:Serotonin; D004247:DNA; D000242:Cyclic AMP; D007545:Isoproterenol; D005459:Fluorides; D010433:Pentylenetetrazole; D004837:Epinephrine