The Linear furanocoumarins psoralen, bergaptren (5-methoxypsoralen), and xanthotoxin (8-methoxypsoralen) have been found in several commonly used vegetables. Although these biosynthetic plant secondary compounds have been used at low concentrations for medical purposes, levels above a certain threshold, as known to occur in some grocery vegetables, are hazardous to human and animal health. High concentrations of these linear furanocoumarins have proven to be carcinogenic, mutagenic, teratogenic, and causal factors of severe photodermatitis. A number of environmental conditions have been shown to increase production of these compounds in plants; however, influence of factors such as cooking temperature and preservatives has not been investigated and will be a primary objective of the proposed study. A number of studies have demonstrated the toxicity of xanthotoxin to animals, but literature on toxicity of psoralen, bergapten or various combinations of the three chemicals is very limited. The mechanism of the toxicity of these combinations to humans or other animals has not been investigated and will be our second major objective. Mice subjects will be used to study distribution, metabolism, and excretion of the chemicals administered by gavage, to assess covalent DNA adducts, to compare target and nontarget tissues for carcinogenesis, and to determine the potential for induction of phase I and/or phase H enzymes by the linear furanocoumarins. The insect Spodoptera exigua will also be used to study the effects of the furanocoumarins on animal growth and reproduction as well as damage to DNA and RNA.
