Retinoids bioassay

Baird, M.B. (1985) Modulation of Chemical Mutagenesis in a Salmonella/Mamalian Tissue Bioassay by Vitamin A and Other Retinoids. This Volume. 

We chose to test our hypothesis using a Salmonella/mammalian microsome test system, since we could utilize this system to isolate the effects of retinoids in modulating the metabolic activation of chemical carcinogens to forms which can covalently interact with bacterial DNA. We also wished to examine, and possibly establish, the limits of usefulness of the widely used Salmonella bioassay in examining the modulation of xenobiotic metabolism by nutritional and other factors. 

In no instance did the synthetic retinoid possess as great an inhibitory capacity as do retinol or retinyl acetate. In addition, the provitamin g-carotene had no effect on mutagenicity of 2-fluorenamine in Salmonella regardless of the carcinogen activation system (Tables III and IV). Thus, 3-carotene would apparently require enzymatic cleavage to vitamin A in order to have an effect in this ijri vitro bioassay and exerts no role by itself in modulating the metabolism of chemical carcinogens in the model system. 

Tables 2-5 list monoterpenoids (Mo), sesquiterpenoids (Sq), diterpenoids (Di), and retinoids (Re), sesterterpenoids (St), meroterpenoids and miscellaneous terpenoids (Me), respectively, discussed in this review. The bioassay systems in which the compounds exhibited inhibitory effects, together with the major sources of the compounds, are included in the Tables. Most of these terpenoids are isolated from natural sources, and their structures are shown in Figs. (2)-(5). Some terpenoids which exhibit significant and/or a broad range of chemopreventive and anti-inflammatory activities are discussed below.

Table 5. Retinoids (Re), Sesterterpenoids (St), and Miscellaneous Terpenoids from Natural Sources and the Bioassay Systems in which the Compounds Exhibited Inhibitory Activities Code Compound Source Occurrence Assay System References...

Frierson MR, Mielach FA, Kochhar DM. Computer-automated structure evaluation (CASE) of retinoids in teratogenesis bioassays. Fundam Appl Toxicol 1990 14 408-28. 

Kochhar, D.M. Penner, J.D. Minutella, L.M. Biotransformation of etretinate and developmental toxicity of etretin and other aromatic retinoids in teratogenesis bioassays. Drug Metab.Dispos., 1989, 17, 618-624... 

In the MDCK cells, treatment with iV-(4-hydroxyphenyl)retinamide did not inhibit arachidonic acid release, suggesting that the retinoid was possibly acting as a cyclooxygenase inhibitor. Whether this enzyme inhibition is related to the retinoid character of the molecule or to a particular spatial configuration of the phenolic end group in the molecule is unknown certainly none of the bioassay systems described in Chapter 5, Vol. 1, point to a different role or mechanism of action for this retinoid as compared to retinoic acid. 

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