Thinner inhalation effects on oxidative stress and DNA repair in a rat model of abuse.

Humans can come into contact with thinner by occupational exposure or by intentional inhalation abuse. Numerous studies of workers for genotoxic effects of thinner exposure have yielded conflicting results, perhaps because co-exposure to variable other compounds cannot be avoided in workplace exposure studies. In contrast, there is no data concerning the genotoxic effects of intentional inhalation abuse. The aim of this project was to examine the genotoxic effects of thinner inhalation in an animal model of thinner abuse (rats exposed to 3000 ppm toluene, a high solvent concentration over a very short, 15 min time period, twice a day for 6 weeks). The data presented here provides evidence that thinner inhalation in our experimental conditions is able to induce weight loss, lung abnormalities and oxidative stress. This oxidative stress induces oxidative DNA damage that is not a characteristic feature of genotoxic damage. No significant difference in DNA damage and DNA repair (biomarkers of genotoxicity) in lymphocytes from thinner-treated and control rats was found. Lead treatment was used as a positive control in these assays. Finally, bone marrow was evaluated as a biomarker of cellular alteration associated with thinner inhalation. The observed absence of hemopoietic and genetic toxicity could be explained in part by the absence of benzene, the only carcinogenic component of thinner; however, benzene is no longer a common component of thinner. In conclusion, thinner did not cause genotoxic effects in an experimental model of intentional abuse despite the fact that thinner inhalation induces oxidative stress.

Systemic toxic effects induced by the aqueous extract of the fire coral Millepora complanata and partial purification of thermostable neurotoxins with lethal effects in mice.

Millepora complanata is a cnidarian widely distributed in the coral reefs of the Mexican Caribbean. This species is popularly known as "fire coral", since contact with it causes severe pain, skin eruptions and blisters. Intravenous administration of of M. complanata aqueous extract induces violent convulsions and death in mice within 1 min (LD50=4.62µgprotein/g of body weight). Doses less than the LD50 produced histopathological damage in kidneys and lungs. Such histopathological damage was completely eliminated after incubation of the extract in heat denaturing conditions. Unexpectedly, the denatured extract conserved its lethal effect. These findings demonstrated that the extract contained hemolytic and phospholipase activities that might be responsible for the histopathological damage, and additionally it contained other unidentified thermostable toxins with lethal effects in mice. Chromatographic analysis of the extract led to the isolation of a 61 kDa vasoconstrictor protein. Furthermore, several non-peptidic vasoconstrictor fractions were separated. Particularly interesting was the fraction MC1-IIA obtained as a result of three-step chromatography processes (ion exchange, gel filtration and reverse phase). Like the original crude extract, this fraction induced vasoconstriction and delayed hemolysis and lethal effects in mice. A subsequent chromatographic analysis of MC1-IIA showed that this fraction contained at least four non-peptidic compounds. MS and NMR spectroscopic data analyses indicated that these metabolites were poly-oxygenated alkylbenzenes. The present study constitutes the first report of the presence of non-peptidic lethal toxins in an organism of the class Hydrozoa, and evidences the great structural diversity of the toxins produced by the Millepora species.