Priming effect of benzo[a]pyrene on monocyte oxidative metabolism: possible mechanisms

Monocytes, separated from human peripheral blood, were preincubated with di fferent polycyclic aromatic hydrocarbons (PAHs) for 24 h and the production of superoxide ions (O-2(.-)) was then measured using as a stimulating agen t phorbol 12-myristate 13-acetate. A significantly enhanced O-2(.-) product ion is only observed when the cells are treated with benzo[a]pyrene (B[a]P) ; benzo[e]pyrene, benzo[a]anthracene and 3-methylcholanthrene induce a smal l but not significant increase of O-2(.-) Anthracene has no effect, while p henanthrene slightly inhibits. The priming activity of B[a]P is unrelated t o variations in intracellular Ca2+ ([Ca2+](i)), as demonstrated by the inab ility of B[a]P to increase [Ca2+](i) concentration in both monocytes and th e promonocytic cell line U937. Furthermore, in monocytes the sarcoplasmic/e ndoplasmic reticulum Ca2+-ATPase inhibitor, thapsigargin, which can increas e [Ca2+](i) evokes a differentiation-like event associated with a decrease in the production of superoxide ions. These results further support that th e enhancing activity of B[a]P on monocytes superoxide production is not med iated by an increase of [Ca2+](i). In contrast, the role of the aryl hydroc arbon receptor (AhR) in B[a]P-induced superoxide ion enhancement is suggest ed by the inhibitory effect of the specific antagonist alpha-naphthoflavone (alpha NF), while the tumor necrosis factor (TNF-alpha) is not involved in the phenomenon. Thus, the interaction of B[a]P with its cytosolic receptor and either the metabolism of the compound into reactive intermediates or t he over-expression of some unknown genes seem to be involved in an essentia l step in this process. (C) 1999 Elsevier Science Ireland Ltd. All rights r eserved.