EFFECTS OF HISTAMINE AND 5-HYDROXYTRYPTAMINE ON THE GROWTH-RATE OF XENOGRAFTED HUMAN BRONCHOGENIC CARCINOMAS

1. The influence of histamine and 5-hydroxytryptamine (5-HT) antagonis ts and agonists on the volume doubling times (Td) of human bronchogeni c carcinomas propagated as s.c. xenografts in immunosuppressed mice wa s examined. 2. The H-2-receptor antagonists, cimetidine and ranitidine , increased Td. 3. Treatment with the H-2-receptor agonist, 4-methyl h istamine, had no effect on Td. 4. Co-administration of 4-methyl histam ine and cimetidine abolished the effects of cimetidine. 5. The 5-HT2-r eceptor antagonists, cinanserin and ketanserin, both increased Td. 6. Treatment with the 5-HT1/2-receptor agonist quipazine (0.1 mg/kg, refl ecting 5-HT2 agonist activity) decreased Td, while a higher dose (10.0 mg/kg) had no effect. 7. The 5-HT1/2-receptor antagonist, methiothepi n, decreased Td. 8. The 5-HT uptake inhibitor, fluoxetine, increased T d in one tumour line but not in another, while the 5-HT releaser/deple tor, fenfluramine, increased Td. 9. Histamine may stimulate tumour gro wth through the histamine H-2-receptor, while the dominant effect of 5 -HT is 5-HT1-receptor inhibition. 10. Tumour growth in some bronchogen ic carcinomas may involve 5-HT uptake mechanisms.