Exposure to bleomycin can result in an inflammatory lung injury. The biological 
effect of this anti-neoplastic agent is dependent on its coordination of iron 
with subsequent oxidant generation. In lung cells, divalent metal transporter 1 
(DMT1) can participate in metal transport resulting in control of an oxidative 
stress and tissue damage. We tested the postulate that metal import by DMT1 
would participate in preventing lung injury after exposure to bleomycin. 
Microcytic anemia (mk/mk) mice defective in DMT1 and wild-type mice were exposed 
to either bleomycin or saline via intratracheal instillation and the resultant 
lung injury was compared. Twenty-four h after instillation, the number of 
neutrophils and protein concentrations after bleomycin exposure were 
significantly elevated in the mk/mk mice relative to the wild-type mice. 
Similarly, levels of a pro-inflammatory mediator were significantly increased in 
the mk/mk mice relative to wild-type mice following bleomycin instillation. 
Relative to wild-type mice, mk/mk mice demonstrated lower non-heme iron 
concentrations in the lung, liver, spleen, and splenic, peritoneal, and liver 
macrophages. In contrast, levels of this metal were elevated in alveolar 
macrophages from mk/mk mice. We conclude that DMT1 participates in the 
inflammatory lung injury after bleomycin with mk/mk mice having increased 
inflammation and damage following exposure. This finding supports the hypothesis 
that DMT1 takes part in iron detoxification and homeostasis in the lung.