Curtis N. Barton

Topical glycolic acid enhances photodamage by ultraviolet light

Background: Alpha‐hydroxy acids (AHAs) are widely used as ingredients in cosmetics. Several studies suggest that AHAs can increase the sensitivity of skin to ultraviolet (UV) light.

Peroxidation of membrane lipids and oxidative DNA damage by fumonisin B1 in isolated rat liver nuclei

Fumonisin B1 (FB1), a contaminant of corn, has been reported to be a hepatocarcinogen in rats. In an attempt to understand its mechanisms of action, a model system of isolated rat liver nuclei was used to determine what effects, if any, FB1 might have on nuclear membrane lipids and DNA. The data suggested that FB1 induced lipid peroxidation concurrently with DNA strand breaks in this in vitro system. Iron and copper had no statistically significant stimulatory effects on these reactions. In addition, the active oxygen scavengers catalase, superoxide dismutase (SOD), mannitol and sodium azide had no significant inhibitory effects on the FB1-induced DNA strand breaks. However, a small but significant reduction in lipid peroxidation by catalase and mannitol was observed. These results suggested that hydroxyl radicals may be the initiators of the nuclear membrane lipid peroxidation, which results in production of peroxyl radicals. In turn, the peroxyl radicals may be responsible for the DNA strand breaks. An alternative explanation is that the hydroxyl radicals, produced close to the DNA-bound metal ions, may induce direct site-specific strand breaks, which are insensitive to the scavengers of active oxygen.

The effects of topically applied glycolic acid and salicylic acid on ultraviolet radiation-induced erythema, DNA damage and sunburn cell formation in human skin.

BACKGROUND alpha-Hydroxy acids (alphaHAs) are reported to reduce signs of aging in the skin and are widely used cosmetic ingredients. Several studies suggest that alphaHA can increase the sensitivity of skin to ultraviolet radiation. More recently, beta-hydroxy acids (betaHAs), or combinations of alphaHA and betaHA have also been incorporated into antiaging skin care products. Concerns have also arisen about increased sensitivity to ultraviolet radiation following use of skin care products containing beta-HA. OBJECTIVE To determine whether topical treatment with glycolic acid, a representative alphaHA, or with salicylic acid, a betaHA, modifies the short-term effects of solar simulated radiation (SSR) in human skin. METHODS Fourteen subjects participated in this study. Three of the four test sites on the mid-back of each subject were treated daily Monday-Friday, for a total of 3.5 weeks, with glycolic acid (10%), salicylic acid (2%), or vehicle (control). The fourth site received no treatment. After the last treatment, each site was exposed to SSR, and shave biopsies from all four sites were obtained. The endpoints evaluated in this study were erythema (assessed visually and instrumentally), DNA damage and sunburn cell formation. RESULTS Treatment with glycolic acid resulted in increased sensitivity of human skin to SSR, measured as an increase in erythema, DNA damage and sunburn cell formation. Salicylic acid did not produce significant changes in any of these biomarkers. CONCLUSIONS Short-term topical application of glycolic acid in a cosmetic formulation increased the sensitivity of human skin to SSR, while a comparable treatment with salicylic acid did not.

In vitro effects of the nephrotoxins ochratoxin A and citrinin upon biochemical function of porcine kidney

Ochratoxin A and citrinin are nephrotoxic mycotoxins found in a variety of foods and feeds. Before studying possible interactions between these two toxins, their individual biochemical effects were examined in vitro by using renal cortical explants derived from male swine of the Hormel-Hanford strain. The following measurements were performed: macromolecule biosynthesis (protein, RNA, and DNA), respiration (14CO2 from [14C]glucose), organic ion (tetraethyl ammonium acetate, i.e., TEA) transport, and membrane perturbation (protein leakage into medium). Levels of the toxins ranged from 0.001 to 1 mM. Ochratoxin A inhibited macromolecule biosynthesis at a lower concentration (0.001 mM) than did citrinin. Protein and DNA synthesis were particularly sensitive to ochratoxin A. Syntheses of protein and DNA were inhibited at ochratoxin A concentrations of 0.01 and 0.001 mM, respectively. RNA synthesis was less sensitive to the mycotoxin; it was inhibited only 60% at 1 mM, the highest concentration of ochratoxin A tested. Citrinin levels of 0.01 mM were required for inhibition of RNA, DNA, and protein synthesis. Inhibition by citrinin was approximately equal for all three classes of macromolecules. Citrinin was more effective than ochratoxin A in the inhibition of respiration and TEA transport; the minimum effective levels of citrinin were 1 and 0.01 mM, respectively. Serious membrane damage as evidenced by increased protein leakage was not caused by either toxin. Stimulation of respiration, perhaps reflective of uncoupling of oxidative phosphorylation, was produced by an ochratoxin A concentration of 1 mM. Inhibition of macromolecule biosynthesis does not seem to be related to the effect of either toxin upon respiration, although a causal relationship between the effects of ochratoxin A on respiration and TEA transport cannot be ruled out.

Upper bound risk estimates for mixtures of carcinogens.

The excess cancer risk that might result from exposure to a mixture of chemical carcinogens usually is estimated with data from experiments conducted on individual chemicals. An upper bound on the total excess risk is estimated commonly by summing individual upper bound risk estimates. The degree to which this approach might overstate the true risk associated with the mixture has not been evaluated previously. This paper reports the results of a Monte Carlo simulation study on the degree of reduction in conservation that might be achieved using alternative methods for calculating mixture upper bounds. An unexpected finding is that for chemicals that exhibit strongly linear dose-response relationships, the summing of multistage-model-based upper bounds on excess risk can be anti-conservative, that is, it can provide less than the nominal 100(1-alpha)% coverage.

PRO-OXIDANT EFFECTS OF THE FLAVONOID MYRICETIN ON RAT HEPATOCYTES IN CULTURE

Myricetin was selected as a model polyphenolic flavonoid for study of its pro-oxidant activity in rat hepatocytes in culture. Its activity was compared with that of a known oxidant, potassium dichromate. Cytotoxicity, membrane lipid peroxidation, and DNA strand breaks were used as endpoints of oxidative cell injury. Myricetin, like potassium dichromate, induced a concentration-dependent increase in cytotoxicity and membrane lipid peroxidation concurrent with a decrease in double-stranded DNA content in cultured rat hepatocytes. However, myricetin was a less potent oxidant than dichromate. Myricetin appears to be less effective in inducing oxidative DNA damage in rat hepatocytes in culture when compared with our previously published studies on isolated rat liver nuclei.

Effects of intermittent exposures of aflatoxin B1 on hepatic and testicular glutathione S-transferase in rats

Glutathione S‐transferase (GST) plays a major role in the detoxification of the potent hepatocarcinogen aflatoxin B1 (AFB1). This study evaluated the effects of intermittent exposures to AFB1 on hepatic and testicular GST in rats. Male Fischer 344 rats were fed diets containing AFB1 (0, 0.01, 0.04, 0.4 and 1.6 ppm) intermittently at 4‐week intervals up to 20 weeks. The control animals were fed an AFB1‐free NIH‐31 diet. Rats consuming diets with 0.01 ppm AFB1 did not show the induction of hepatic or testicular GST activity. Intermittent exposures to AFB1 at concentrations of 0.04–1.6 ppm significantly increased the GST activities. The increase of the enzyme activity was proportional to the dose and length of AFB1 exposure. Copyright