Polycyclic aromatic hydrocarbon coated onto Fe(2)O(3) particles: assessment of cellular membrane damage and antioxidant system disruption in human epithelial lung cells (L132) in culture.

The aim of this study was to investigate the oxidative effects of Fe(2)O(3), benzo(a)pyrene (B(a)P) and pyrene, alone or in association (B(a)P or pyrene coated onto Fe(2)O(3) particles), in normal human embryonic lung epithelial cells (L132) in culture. We evaluated: (i) membrane integrity, through fatty acid release (stearic acid, oleic acid, linoleic and linolenic acids, homolinolenic acid, arachidonic acid) and malondialdehyde (MDA) production; and (ii) antioxidant status, through enzymatic and non-enzymatic antioxidant defenses (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione status, beta-carotene). Fe(2)O(3) did not induce any change in L132 cells. In pyrene-treated cells, SOD induction (P<0. 05), glutathione oxidation (P<0.05) and beta-carotene consumption (P<0.001) may counteract free radicals (FR)-induced damage. However, in B(a)P-incubated cells, SOD inactivation (P<0.05), GR increases (P<0.05), glutathione oxidation (P<0.05) and beta-carotene decreases (P<0.001) showed high disruption of antioxidants, thereby allowing FR-induced damage (i.e. arachidonic acid release, P<0.01; MDA production, P<0.01). Our main finding was that both associations caused higher FR-induced damage (i.e. MDA production, P<0.001; SOD inactivation, P<0.01) than either chemical alone. Several mechanisms could account for this result: enhanced uptake of Fe(2)O(3) particles and/or greater availability of polycyclic aromatic hydrocarbons (PAHs). We hypothesized also that Fe(2)O(3) and polycyclic aromatic hydrocarbons are more deleterious by virtue of their associations being able to produce higher oxidative effects than either chemical alone.

Peripheral markers (Clara cell protein and alpha-glutathione S-transferase) and lipidoperoxidation (malondialdehyde) assessment in Sprague-Dawley rats instilled with haematite and benzo[a]pyrene.

The literature suggests that the concomitant exposure to polycyclic aromatic hydrocarbons (PAH) and ferric oxide particles could enhance lung cancer incidence in environmental and occupational settings. High levels of tracheobronchial tumours were obtained in hamsters exposed to benzo[a]pyrene (B[a]P) adsorbed onto ferric oxide carrier particles. Therefore, we have assessed the toxic effects of exposure to haematite (Fe2O3) and B[a]P in male Sprague-Dawley rats. Animals were instilled with the chemicals alone (3 mg of Fe2O3 or B[a]P) or in combination (3 mg Fe2O3 + 3 mg B[a]P). Bronchoalveolar lavages (BAL) and biological samples (serum and urine) were collected 48 h after the intoxication. Clara cell protein (CC16) and alpha-glutathione S-transferase (alpha-GST), as peripheral markers of both tracheobronchial epithelial cell integrity and renal dysfunction, were determined in BAL fluid, serum and urine. Malondialdehyde (MDA), a marker of lipid peroxidation, was measured in BAL fluid and serum. We observed a significant increase of CC16 concentrations in BAL fluid after Fe2O3 + B[a]P instillation (p < 0.05) in serum after Fe2O3 and Fe2O3 + B[a]P exposure (p < 0.01) and in urine after B[a]P administration (p < 0.01). Instillation of Fe2O3 + B[a]P produced an increased amount of alpha-GST in BAL fluid (p < 0.01), whereas B[a]P alone caused a significant elevation of alpha-GST in serum and urine (p < 0.01). Moreover, Fe2O3 or Fe2O3 + B[a]P instillation induced a significant increase in MDA levels in BAL fluid (p < 0.01 and p < 0.05). In conclusion, Fe2O3 may have a low pulmonary toxicity. However, B[a]P manifested a rapid and high toxicity in the respiratory tract and kidneys. When B[a]P was adsorbed on haematite particles, both its retention in the respiratory tract and pulmonary toxicity increased.