The effects of calcium antagonists on anthrone skin tumor promotion and promoter-related effects in SENCAR mice.
The present study investigated a possible role for Ca2+ in skin tumor promotion by anthrones. This was accomplished by testing the effects of two Ca2+ antagonists, verapamil and 3,4,5-trimethoxybenzoic acid 8-(diethylamino) octyl ester (TMB-8), on tumor promotion and promoter-related effects induced by the anthrone chrysarobin in SENCAR mice. Verapamil and TMB-8 both effectively inhibited epidermal ornithine decarboxylase (ODC) induction by a single application of chrysarobin. Both Ca2+ antagonists inhibited anthrone-induced skin edema and epidermal hyperplasia. Additionally, both verapamil and TMB-8 slightly inhibited (20-21% at the highest doses) tumor promotion with chrysarobin. Although the inhibition by both Ca2+ antagonists was not statistically significant (P > 0.05) in either case, the fact that both compounds produced a similar inhibition suggests that this effect may be biologically relevant. Collectively, the data suggest a possible role for Ca2+ in the process of skin tumor promotion by anthrones.
Battalora
M S
MS
Department of Carcinogenesis, University of Texas, M.D. Anderson Cancer Center, Smithville 78957, USA.
Johnston
D A
DA
DiGiovanni
J
J
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000873:Anthracenes / Q000633:toxicity*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity*; D004487:Edema / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006965:Hyperplasia / Q000201:enzymology; D051379:Mice; D018632:Mice, Inbred SENCAR; D065108:Ornithine Decarboxylase Inhibitors; D010212:Papilloma / Q000139:chemically induced / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000201:enzymology / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D018709:Statistics, Nonparametric; D014700:Verapamil / Q000494:pharmacology
D000873:Anthracenes; D002121:Calcium Channel Blockers; D002273:Carcinogens; D065108:Ornithine Decarboxylase Inhibitors; D017382:Reactive Oxygen Species; D015127:9,10-Dimethyl-1,2-benzanthracene; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; C013883:chrysarobin; D005707:Gallic Acid; D014700:Verapamil; D002118:Calcium