Rat lung metallothionein and heme oxygenase gene expression following ozone and zinc oxide exposure.
We have conducted exposures in rats to determine pulmonary responses following inhalation of two common components of welding fumes, zinc oxide and ozone. To examine their effects on target-inducible gene expression, we measured mRNA levels of two metal-responsive genes, metallothionein (MT) and heme oxygenase (HO), in lung tissue by RNA slot-blot analysis. A 3-hr exposure to ZnO fume via a combustion furnace caused a substantial elevation in lung MT mRNA at all concentrations tested. Exposures to 5 and 2.5 mg/m3 ZnO resulted in peak 8-fold increases in MT mRNA levels (compared to air-exposed control animal values) immediately after exposure, while 1 mg/m3 ZnO exposure caused a 3.5-fold elevation in MT mRNA. These levels returned to approximate control gene expression values 24 hr after exposure. In addition, ZnO exposure caused an immediate elevation in lung HO gene expression levels, with 8-, 11-, and 5-fold increases observed after the same ZnO exposure levels (p < 0.05). Like MT gene induction, HO mRNA values returned to approximate control levels 24 hr after exposure. In striking contrast to the induction of MT and HO gene expression after ZnO exposures, there was no elevation in gene expression following a 6-hr exposure to 0.5 and 1 ppm ozone, even when lungs were examined as late as 72 hr after exposure. Our results demonstrate the induction of target gene expression following the inhalation of ZnO at concentrations equal to, and below, the current recommended threshold limit value of 5 mg/m3 ZnO. Furthermore, the lack of effect of ozone exposure on MT and HO gene expression suggests no involvement of these genes in the acute respiratory response to this oxidant compound.
Cosma
G
G
Institute of Environmental Medicine, New York University Medical Center, New York 10016.
Fulton
H
H
DeFeo
T
T
Gordon
T
T
D000280:Administration, Inhalation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000235:genetics*; D015151:Immunoblotting; D008168:Lung / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics*; D016273:Occupational Exposure; D010126:Ozone / Q000633:toxicity*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015533:Transcriptional Activation; D015034:Zinc Oxide / Q000633:toxicity*
D012333:RNA, Messenger; D010126:Ozone; D008668:Metallothionein; D006419:Heme Oxygenase (Decyclizing); D015034:Zinc Oxide