Autoradiographic and histopathologic studies on the mode of action of an aromatic retinoid (Ro 10-9359) on chemically induced epithelial tumors in Swiss mice.
The mode of action of an aromatic analogue of retinoic acid, ethyl all-trans-9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoate (Ro 10-9359), a compound known to possess a considerable prophylactic and therapeutic effect on skin papillomas and carcinomas, was investigated with autoradiographic and histopathologic methods. The ip application of a single dose of 1,000 mg Ro 10-9359/kg to female Swiss mice with chemically induced skin papillomas caused a 29% regression of the mean tumor diameter after 3 days and a 51% regression after 7 days. In the tumors, the number of DNA-synthesizing cells [measured by the labeling index (LI)] and the length of the cell cycle were not affected by the retinoid; thus a mode of action at the level of cell proliferation can be excluded. In the normal skin, an increase in the LI of about 30% was observed. A small effect on the cell loss was observed; however, it was not sufficient to explain quantitatively the regression of the tumors. When measured histometrically, it appeared that the loss of the horn and the formation of necroses, 3-10 times larger than in the placebo groups, were mainly responsible for the tumor regressions caused by the retinoid. After 7 days, the proportion of stroma in the tumors was increased, and dilation of the vessels and edema in the stroma proximal to the necroses were frequent.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002455:Cell Division; D003436:Croton Oil; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005260:Female; D051379:Mice; D009336:Necrosis; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010212:Papilloma / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014801:Vitamin A / Q000031:analogs & derivatives*
D004273:DNA, Neoplasm; D014801:Vitamin A; D014212:Tretinoin; D015127:9,10-Dimethyl-1,2-benzanthracene; D003436:Croton Oil