EFFECT OF ARSENIC EXPOSURE ON ALVEOLAR MACROPHAGE FUNCTION .2. EFFECTOF SLIGHTLY SOLUBLE FORMS OF AS(III) AND AS(V)

The pulmonary toxicity of a substance depends on a number of chemical and physical characteristics, including the solubility of the compound s. In the lung, insoluble forms of metals may be more tumorigenic than soluble forms despite the fact that this effect has not been quantita ted and the mechanism of action has not been elucidated. The toxic eff ects of slightly soluble forms of As(III) and As(V) were evaluated by determining alteration in function of pulmonary alveolar macrophages ( PAM) following in vivo and in vitro exposure. Male Sprague-Dawley rats were used throughout. Twenty-four hours following intratracheal insti llation of 1 mg/kg (as arsenic) of either arsenic trisulfide (As(III)) or calcium arsenate (As(V)), PAM were lavaged and analyzed for altera tions in superoxide (O-2(-)), and tumor necrosis factor (TNF-alpha) pr oduction. There were no differences in bronchoalveolar lavage fluid TN F-alpha. PAM. lavaged from As(V)-exposed animals showed significant in creases in O-2(-) production and in basal release of TNF-alpha. PAM la vaged from animals receiving As(III) did not show significant alterati ons. To test the direct effects of arsenic, PAM were lavaged from cont rol animals and exposed to concentrations of 0,1 to 300 mu g/ml arseni c in vitro for up to 24 hr. Doses used were not cytotoxic to PAM, sinc e LDH release was not significantly increased. Significant dose-depend ent inhibition of O-2(-) production was only evident after 24 hr expos ure to arsenicals. Both As(III) and As(V) produced inhibition at conce ntrations of 10 mu g/ml. Suppression of LPS-induced release of TNF-alp ha also occurred at similar concentrations for both arsenicals (4-5 mu g/ml). Neither arsenical inhibited prostaglandin E(2) production. Mea surement of soluble arsenic concentrations indicated dissolution of th e compounds could not account for all of the effects seen. Arsenic-ind uced alteration in PAM function may compromise host defense. (C) 1995 Academic Press, Inc.