The psoralens are naturally occurring plant metabolites found in common fruit and vegetable crops. Synthetic forms of 8-methoxypsoralen (xanthotoxin or methoxsalen) and 5-methoxypsoralen (bergapten) are widely used as drugs in skin photochemotherapy (PUVA) and have been used as tanning activators in many sunscreen preparations. Unfortunately, PUVA has been shown to have major side effects. For example, malignant melanoma. Induced abortions, and spontaneous abortions have been reported in patients under PUVA. An increase in low birthweight infants has also been reported. Recent studies have shown that the psoralens have adverse reproductive effects in rats. Therefore, these chemicals could also represent a risk for infertility or birth defects in humans.
Dr. Moussa Diawara
Entomology and Toxicology

Comet Assay result (click image for larger view)
The study uses the following methodologies. Each psoralen will be administered orally or by injection in male and female wistar rats during acute and subchronic tests. Its effects will be observed in tissue culture and in vitro experiments. Its impact on secretion of reproductive hormones, gene expression, and gonadal function will also be determined.

The Specific Aims are to:
I) investigate the direct effect of xanthotoxin or bergapten dosing on the hypothalamo/pituitary axis in female and male rats,
II) investigate the direct effect of xanthotoxin or bergapten dosing on gonadal function in female and male rats, and III) investigate the role of the male in xanthotoxin- or bergapten-induced pregnancy effects.
The results of the proposed study will help a) establish the role of the hypothalamo-pituitary-gonadal axis in the response of the reproductive system to environmental insults such as the psoralens; b) provide dramatic insight into the potential reproductive toxicity of the psoralens in female and male reproductive systems; c) better understand gender differences in the response of the male and female reproductive systems to xenobiotic exposures; and d) reduce the risk in women and men who are exposed to therapeutic (medicinal use), dietary (produce handling and/or consumption), cosmetic (sunscreen use), or occupational (agricultural or industrial work) psoralens.
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