Toxicity linear furanocoumarins

Phytoalexins are low molecular weight compounds produced in plants as a defense mechanism against microorganisms. They do, however, exhibit toxicity to humans and other animals in addition to microbes (30). Coumarins, glycoalkaloids, isocoumarins, isoflavonoids, linear furanocoumarins, stilbenes, and terpenes aU. fall into the category of phytoalexins (31). Because phytoalexins are natural components of plants, and because their concentration may increase as a response to production and management stimuli, it is useful to recogni2e the possible effects of phytoalexins in the human diet. 

Because the resistance of polyxenes to the toxic effects of linear furanocoumarins apparently does not extend to the angular furanocoumarins (22), we have undertaken comparative metabolic fate studies with a representative of each of these furanocoumarin classes. Tritlated psoralen or isopsoralen (Figure 1) was administered as before to last stage polyxenes caterpillars, and the distribution, elimination, and biochemical fate of the compounds determined (28). 

Our studies with polyxenes caterpillars and radiolabeled furanocoumarins have provided what appears to be a definitive explanation of the apparent total Insensitivity of these insects to the toxic effects of linear furanocoumarins present in their... 

Our studies indicate that rapid metabolic detoxification of linear furanocoumarins is an effective resistance mechanism for K polyxenes against the toxic effects of these compounds. It has been postulated that the adaptation of some plants to produce angular furanocoumarins was in response to the reduced effectiveness of the linear furanocoumarins as deterrents for herbivores such as polyxenes (22). Such may Indeed be true, but our studies on the comparative detoxification of linear and angular furanocoumarins suggest that, at best, the presence of angular furanocoumarins in plants confers only a tenuous margin of relative "safety" against polyxenes. 

Insect herbivory is an important selective force in the ecology and evolution of plants. The linear furanocoumarin, xanthotoxin (19), found in many plants of die Apiaceae and Rutaceae is toxic to the larvae of Spodoptera eridania, a generalist insect herbivore. This toxicity was shown to be increased in the presence of UV light. 

Butterflies of the genus Papilio (Lepidoptera) often are associated with members of the Apiaceae. Xanthotoxin (19), a linear furanocoumarin, occurs in many plants of the Apiaceae. This compound is not appreciably toxic to the larvae of Papilio polyxenes which normally feed on umbelliferous plants. Most of these insects feed only on plants that have linear furanocoumarins and, in general, do not consume plants that make angular furanocoumarins. Angelicin (30)... 

The acetylenes and linear furanocoumarins (psoralens) are examples of bioactive secondary metabolites that have been considered undesirable in plant foods due to their toxic effects. Some acetylenes are known to be potent skin sensitizers and irritants, and neurotoxic in high concentrations, but have also been shown to have a pronounced selective cytotoxic activity against various cancer cells. Due to their role in plant defence many acetylenes and psoralens are considered natural pesticides or in some cases phytoalexins since their formation is often induced in plants as a response to external stimuh. Psoralens are photoactivated secondary metabolites that have been used since ancient times to treat human skin disorders. However, the use of these furanocoumarins in medicine has been associated with increased incidence of skin cancer, and a number of studies have also demonstrated that the furanocoumarins can be carcinogenic, mutagenic, photodermatitic and to have reproductive toxicity. 

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