Evaluation of the cytotoxicity of dihydroxytryptamines and 5-hydroxytryptamine antagonists as cytotoxic agents in dimethylhydrazine-induced adenocarcinomata.
The cytotoxicity of 5,6-dihydroxytryptamine (5,6-DHT), 5,7-dihydroxytryptamine (5,7-DHT), bromolysergic acid diethylamide (BOL), methysergide, and cyproheptadine, and also of 5,6-DHT together with either BOL, methysergide, or cyproheptadine in dimethylhydrazine-induced (DMH) carcinomata of rat colon was evaluated by estimating the percentage of necrotic cells in histological sections of tissues taken 15 h after injection of each of the drugs. In addition, the influence of methysergide and cyproheptadine on the tumour cell mitotic rate was estimated by means of a stathmokinetic technique. Both 5,6-DHT and 5,7-DHT were cytotoxic at each dose tested and for each of these agents the percentage of necrotic cells was directly correlated with the dose of drug used. BOL was not found to be cytotoxic to the colonic carcinomata, whereas both methysergide and cyproheptadine did cause detectable tumour cell necrosis. Methysergide was also found to accelerate tumour cell proliferation, whereas cyproheptadine did not. BOL competitively inhibited the cytotoxicity of 5,6-DHT and neither methysergide nor cyproheptadine potentiated the effect of 5,6 DHT.
D015115:5,6-Dihydroxytryptamine / Q000494:pharmacology*; D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000230:Adenocarcinoma / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003533:Cyproheptadine / Q000494:pharmacology; D004102:Dihydroxytryptamines / Q000494:pharmacology*; D004127:Dimethylhydrazines / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004102:Dihydroxytryptamines; D004127:Dimethylhydrazines; D012702:Serotonin Antagonists; D003533:Cyproheptadine; D015116:5,7-Dihydroxytryptamine; D008238:Lysergic Acid Diethylamide; D015115:5,6-Dihydroxytryptamine; D008784:Methysergide