Carol S. Jones

Dietary retinoic acid inhibits mouse skin carcinogenesis irrespective of age at initiation

In the two-stage protocol of skin carcinogenesis, the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) is applied to the skin of mice at around seven weeks of age. We previously performed DMBA initiation at three weeks of age to study the effect of pharmacological (30 micrograms/g diet) dietary retinoic acid (RA) on skin carcinogenesis. In this study we asked whether dietary pharmacological RA is equally effective against skin carcinogenesis when mice are initiated with (DMBA) at 7 weeks of age and then subjected to weekly applications of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or mezerein (MEZ) for 20 weeks. Similar to the three-week initiation protocol, high dietary RA inhibited papilloma incidence and yield in MEZ- but not in TPA-promoted female SENCAR mice. In addition, carcinoma incidence and yield were decreased by high dietary RA in TPA- as well as MEZ-treated mice. These data demonstrate that the high dietary RA diet is as effective in inhibiting papilloma and carcinoma formation when the DMBA is applied at seven weeks of age as at three weeks.

Retinol and β‐carotene concentrations in skin, papillomas and carcinomas, liver, and serum of mice fed retinoic acid or β‐carotene to suppress skin tumor formation

Abstract Using 7,12‐dimethylbenz[a] anthracene as the initiator and 12‐O‐tetradecanoyl‐13‐acetate as the tumor promoter on the dorsal skin of Sencar mice, we previously showed that pharmacological dietary all‐trans‐retinoic acid and β‐carotene inhibit the conversion of papillomas to carcinomas in a two‐stage system of chemical carcinogenesis. The purpose of this study was to determine the influence of dietary retinoic acid and β‐carotene on retinoidand β‐carotene concentrations in skin and other tissues. We were unable to measure tissue retinoic acid because of the relatively limited amount of tissue available for analysis and the fast rate of metabolism. Different dietary levels of retinoic acid or β‐carotene did not influence total retinol of skin, papilloma, and carcinoma tissues, which all showed a concentration of approximately 1 ± 0.5 μg/g wet wt. Equally refractory to dietary retinoic acid or β‐carotene was serum retinol concentration. In contrast, dietary retinoic acid protected loss of liver reti...

Cyclic AMP and Microtubular Dynamics in Cultured Mammalian Cells

The discovery, announced simultaneously by the laboratory of Dr. Pastan (1) and by ourselves (2) of profound change in cell habitus produced by dibutyryl cyclic AMP, appears to hold important implications for the field of cellular interactions generally and the nature of malignancy specifically. The reaction under consideration here resembles in many respects the changes produced when a cell is transformed to malignancy by an oncogenic virus or chemical agent. However, in contrast to the irreversible nature of the latter set of changes, that produced by cyclic AMP is completely reversible. It thus appears to furnish an ideal tool for study of the molecular nature of the underlying effects.

Dietary retinoids are essential for skin papilloma formation induced by either the two-stage or the complete tumorigenesis model in female SENCAR mice

Our previous work has shown that dietary retinoic acid (RA) is necessary for skin tumor formation induced by the two-stage protocol with the initiator 7,12-dimethylbenz[a]anthracene (DMBA) and the promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA) (De Luca et al., Cancer Res., 36 (1976) 2334-2339). Here we report that retinoids are required for tumorigenesis by the two-stage as well as by the complete tumorigenesis protocol. Mice were treated with a single dose of DMBA (20 micrograms), followed by 20 applications of TPA (2 micrograms), or by 20 applications of DMBA (25 micrograms for 2 weeks and 51 micrograms thereafter). Regardless of the tumor induction protocol, tumor formation was inhibited by vitamin A-deficiency, while RA (3 micrograms/g of diet) or retinyl palmitate (RP, 6 micrograms/g) supplementation permitted the appearance of tumors. In addition, in comparison to the purified diets and regardless of their RA levels, the non-purified Purina chow diet enhanced tumor yield especially in the two-stage tumorigenesis protocol. This effect was less striking in mice with tumors induced by the complete tumorigenesis protocol. In summary, dietary retinoids are essential for skin tumor formation induced either by the two-stage or the complete tumorigenesis protocol.