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The role of heme oxygenase (HO)-1 was evaluated in the oxygen-resistant hamster fibroblast cell line, O 2 R95, which moderately overexpress HO when compared with the parental cell line, HA-1. To suppress HO-1 expression, O 2 R95 were transfected with HO-1 antisense oligonucleotide or treated with tin-mesoporphyrin (SnMP). To increase HO-1 expression, cells were transfected with HO-1 cDNA in a pRC/cytomegalovirus (CMV) vector. All cells were challenged with a 48-h exposure to 95% O 2 (hyperoxia). When HO activity was suppressed, O 2 R95 cells had significantly decreased cell viability, increased susceptibility to lipid peroxidation, and increased protein oxidation in hyperoxia. In contrast, further overexpression of HO-1 did not improve resistance to oxygen toxicity. Antisense-transfected cells and SnMP-treated cells with lowered HO activity showed increased levels of cellular heme compared with controls. In the HO-1 cDNA-transfected O 2 R95 cells, cellular heme was lowered compared with controls; however, cellular redox active iron levels were increased. We conclude that HO mediates cytoprotection to oxygen toxicity within a narrow range of expression. We speculate that this protective effect may be mediated in part through increased metabolism of the pro-oxidant heme but that higher levels of HO activity obviate protection by increased redox active iron release.Heme oxygenase (HO-1), 1 the rate-limiting enzyme in the conversion of heme to bilirubin, is known to be induced by various oxidant stresses. However, it is not clear whether HO serves in protection against hyperoxia and, if so, by which mechanisms. HO-1 antisense transfection experiments have shown that higher HO-1 protein levels were associated with protection against UVA radiation (1). Furthermore, transfection of coronary vessel endothelial cells with an overexpression vector containing HO-1 cDNA resulted in resistance against hemoglobin-induced injury (2). We have previously shown that HA-1 hamster fibroblasts made stably resistant to oxygen toxicity (O 2 R95) had 1.8-fold higher HO activity (3), suggesting that moderate increases in HO activity may be beneficial in resistance to oxygen toxicity. However, O 2 R95 cells have increases in other antioxidants that may also contribute to their resistance to oxygen toxicity (4), and no direct evidence currently exists linking HO to resistance to oxygen toxicity.Investigators have hypothesized that HO may serve a role in protection against oxidative injury by forming the antioxidant molecules biliverdin and bilirubin (5, 6). Additionally, induction of ferritin with enhanced HO activity has been observed (1). This could lead to sequestration of redox active iron, thereby conferring protection against oxidative stress (7). Another possible antioxidant mechanism of HO could involve the destruction of heme itself. Heme and hemoproteins have been shown by several investigators to be instrumental in exacerbating oxidative injury (8, 9). This has lead to the hypothesis that reduction of the cellular heme pool by ...

The U.S. Department of Justice (DOJ) mail facility in Landover, Maryland, was contaminated with Bacillus anthracis spores as a result of the 2001 anthrax bioterrorism attacks through the U.S. postal system. Surface environmental sampling within the facility indicated that the contamination was due to receipt of mail that had come in contact with Bacillus anthracis spores from the source letters at the Brentwood postal facility in Washington, DC. The DOJ adopted a two-pronged approach for remediating the facility, using aqueous chlorine dioxide to decontaminate hard, nonporous surfaces and paraformaldehyde to fumigate two pieces of mail equipment. Before the start of the remediation activities, all porous materials were removed from the mail area. Since all postremediation environmental samples were negative for growth of Bacillus anthracis spores, the remediation was judged to be effective. The facility remained closed for almost 4(1/2) months. The cleanup activities took about 2(1/2) months, with source reduction activities being the most time-consuming. Of the seven facilities that performed fumigations to remediate Bacillus anthracis contamination, the DOJ mail facility was the second building to be reopened.

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