Enhancement of tumor growth by drugs with some common molecular actions.
A group of structurally related drugs representing diverse therapeutic classes share, among a number of pharmacological properties, enhancement of tumor growth in several rodent models of malignancy. One common action, the inhibition of histamine binding to and catalytic activity of cytochrome P450 monooxygenases, is highly correlated with potency to enhance tumor growth. Among members of this drug ensemble, the antiestrogen tamoxifen has been shown in controlled clinical studies to increase the incidence of uterine and gastrointestinal cancer and to accelerate the course of gastric cancer, and the tamoxifen analogue clomiphene has been linked to neuroblastoma and the tricyclic group of antidepressants to ovarian cancer. The determination of drug affinities for protein modulators of cell growth, proliferation, and transformation suggests a strategy for identifying at least some classes of chemicals that impart oncologic risks to humans.
LaBella
F S
FS
Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
Brandes
L J
LJ
D000818:Animals; D000928:Antidepressive Agents / Q000633:toxicity*; D014150:Antipsychotic Agents / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000633:toxicity*; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced* / Q000473:pathology*; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000633:toxicity*
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D002273:Carcinogens; D006634:Histamine H1 Antagonists; D013629:Tamoxifen