David H. Reese

Rapid induction of alkaline phosphatase activity by retinoic acid.

Abstract Retinoic acid (vitamin A acid) increased alkaline phosphatase activity in cultured cells derived from both normal rat prostate and the Dunning R-3327 transplantable prostatic adenocarcinoma. Retinoic acid was found to be 3–4-fold more effective as an inducer of enzyme activity than retinol or retinal. In one rapidly-growing cell line (UMS-1541Q) which has a barely-detectable level of enzyme activity in the uninduced state, increased activity could be detected as early as 3–4 hours after the addition of 10μM retinoic acid. This increase was totally blocked by actinomycin D and cycloheximide. The demonstrated rapid inducibility of alkaline phosphatase activity provides a specific marker for the action of retinoic acid at the molecular level.

Evidence for the retinoid control of urothelial alkaline phosphatase

Abstract The amount of alkaline phosphatase activity per μg of DNA in the urothelium (transitional epithelium) of the rat urinary bladder, organ-cultured in chemically-defined serum-free medium, decreased greater than 70% during a 13 day culture period. This decrease in enzyme activity corresponded inversely with the increase in cell number in the urothelium indicating that enzyme synthesis did not accompany growth. Alkaline phosphatase activity was increased back to values approaching normal enzyme levels during a 3 day culture period by the addition of 10 μM retinoic acid. Retinol also increased enzyme activity but it was only half as effective as retinoic acid. A significant increase in enzyme activity was initiated by 1 μM retinoic acid, however the most effective concentration was at 10 μM.

A rationale for the loss of growth control during experimental bladder carcinogenesis

A rationale is presented which provides an explanation for the loss of growth control which is associated with the early phase of experimentally-induced bladder cancer. Two early events which occur in the urothelium following exposure to carcinogen, the focal loss of alkaline phosphatase activity and the initiation of cell proliferation, are both proposed to be the result of a defect in the interaction between glucocorticoid hormone and urothelium. The possible causes for this defect are discussed in terms of a defect in, or an interference with, the glucocorticoid-receptor mechanism.

Focal Suppression and Induction of Hyperplasia by the Bladder Carcinogens Butyl(4-hydroxybutyl)nitrosamine and Butyl(3-carboxypropyl)nitrosamine in Organ-Cultured Rat Bladder Epithelium

The effects of the bladder carcinogens butyl(4-hydroxybutyl)nitrosamine (BBN) and butyl(3-carboxypropyl)-nitrosamine (BCPN) on proliferating transitional rat epithelium in organ culture were studied. At low to intermediate concentration ranges (0.5--2.9 mM), both compounds appeared to stimulate hyperplasia in some regions of epithelia. The major effect of both carcinogens, however, was to suppress hyperplasia in other regions of epithelia and, at higher concentrations (5--6 mM), to cause necrosis. For comparable concentrations, BBN was more effective in suppressing proliferation and causing necrosis than was BCPN.