retinol-acetate and Hyperplasia

Prostatic epithelium proliferates in a defined medium consisting of basal medium RPMI1640 containing transferring (1 microgram/ml), EGF (10 ng/ml), and insulin (3.7 micrograms/ml or 0.1 IU/ml). Although neither dexamethasone nor retinyl acetate affected the proliferation of prostatic epithelium in RPMI1640 containing transferrin alone, they modify the mitogenic effect of EGF and insulin. Dexamethasone at 10(-10) M or retinyl acetate at about 3 X 10(-9) M inhibits proliferation stimulated by EGF. Higher concentrations of dexamethasone (10(-8) - 10(-6) M) or retinyl acetate (3 X 10(-8) - 10(-7) M) enhance the mitogenic activity of EGF. Dexamethasone had a similar effect in the presence of insulin. However, retinyl acetate stimulated, but did not significantly inhibit, proliferation in the presence of insulin. These results suggest that both dexamethasone and retinyl acetate, and possibly other glucocorticoids and retinoids, may regulate the proliferation of prostate epithelium by a dose-dependent modification of the activity of insulin and EGF.

Topics: Aged; Cell Division; Culture Media; Dexamethasone; Diterpenes; Dose-Response Relationship, Drug; Drug Interactions; Epidermal Growth Factor; Epithelium; Humans; Hyperplasia; Insulin; Insulin Antagonists; Male; Middle Aged; Prostate; Retinyl Esters; Vitamin A

The role of vitamin A in the induction and growth of chemically induced tumors is still controversial. While in some studies vitamin A influenced inhibition of chemically induced tumors was observed, other studies report on an enhancing influence of this substance on tumor induction. The cheek pouch epithelium of sixty five Syrian golden hamsters was exposed to DMBA and different doses of retinyl acetate, singly and in combination with DMBA. The findings suggest that 1) a significant delay occurs in tumor induction in animals treated with DMBA in combination with a higher concentration (2.0%) of retinyl acetate, 2) retinyl acetate at lower concentration (0.5 and 1.0%) does not inhibit or delay tumor induction.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Benz(a)Anthracenes; Cheek; Cricetinae; Diterpenes; Female; Hyperplasia; Male; Mesocricetus; Mouth Mucosa; Mouth Neoplasms; Retinyl Esters; Time Factors; Vitamin A

Tumor initiation by topical application of 7,12-dimethylbenz[a]anthracene (DMBA) in dimethyl sulfoxide (DMSO) followed by topical application of retinyl acetate (RA), ethylphenylpropiolate, or acetic acid in DMSO at inflammatory and hyperplasiogenic dose regimens caused the rapid promotion of fibrovascular polyps with dysplastic epithelium in hamster cheek pouch. Such lesions did not occur in control animals initiated with DMBA followed by application of DMSO only, where inflammation was also minimal. At the dose regimen employed, RA caused obvious cytotoxicity and tissue destruction. With EPP and AA, there was no histological evidence of tissue destruction. At dose regimens resulting in minimal inflammation and no apparent cytotoxicity, RA promoted almost no polyps, but a higher yield of other tumor types. Thus, inflammation and/or hyperplasia apparently exerted a strong polyp-promoting and progressive influence. This and other differences between the tumorigenic responses of hamster-pouch mucosa and mouse skin suggest that the former supplement the latter in carcinogenic risk assessment.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Acetates; Alkynes; Animals; Carcinogens; Cheek; Cricetinae; Diterpenes; Hyperplasia; Mice; Neoplasms, Experimental; Polyps; Retinyl Esters; Vitamin A

The administration of a 250-ppm retinyl acetate dietary supplement for various periods relative to intragastric administration of 50 mg benzo[a]pyrene (BP) significantly inhibited the induction of mammary cancers in virgin female inbred LEW/Mai rats. with day of BP administration taken as time 0, groups receiving the retinoid from weeks -2 to +1, +1 to +90, +20 to +90, and -2 to +90 showed a significant reduction in tumor response as compared to controls. The inhibition of carcinogenesis achieved by a +1 to +20 administration schedule was temporary; the tumor yield was suppressed initially but returned to control levels by week 60. Autoradiographic analysis of mammary glands from 50-day-old rats indicated that a 2-week exposure to supplemental retinyl acetate significantly reduced the mammary gland parenchymal cell labeling index in ductal, alveolar, and terminal end bud structures. Beginning the retinyl acetate supplement 1 week after the administration of BP significantly reduced the number of terminal ductal hyperplasias. The inhibition of carcinogenesis achieved by a short period of retinyl acetate administration before and during the period of carcinogen availability as well as the inhibition achieved by long-term postcarcinogen retinoid exposure may involve an antiproliferative effect on the rat mammary gland.

Topics: Animals; Benzopyrenes; Body Weight; Cell Division; Diet; Diterpenes; Female; Hyperplasia; Intubation, Gastrointestinal; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Precancerous Conditions; Rats; Rats, Inbred Lew; Retinyl Esters; Vitamin A