Environmental Engineering Reference
In-Depth Information
DMT-1-defi cient rats had signifi cantly higher levels of both Fe and V in their lungs
than did controls, and exhibited signifi cantly more lung damage. The results suggest
a protective transport role for DMT-1 in rat lung tissue. In normal Sprague-Dawley
rats instilled with Fe or V, immunohistochemistry results demonstrate that Fe induced
DMT-1 in lungs, whereas V had the opposite effect. The normal Sprague-Dawley
rats that were pre-exposed to Fe and later challenged with 500
g of ROFA exhibited
better metal clearance than those pre-treated with saline. However, rats pre-exposed
to V had signifi cantly less metal clearance 15 min after exposure to ROFA than did
controls (no p value given), although the effect of V pre-exposure was not signifi -
cantly different than saline from 30 to 60 min post exposure to ROFA. Lung injury/
infl ammation was greater in the lungs of animals pre-exposed to V (no p value
given), suggesting down-regulating effects on metal clearance by V. To evaluate
expression of DMT-1, BEAS-2B cells were incubated with either culture medium,
100
ʼ
M V, and were then evaluated using RT-PCR and Western blot
analysis. In vitro and in vivo results were similar. This study suggested that lung
metal clearance is negatively affected by exposure to V, which is commonly found in
ROFA particles, potentially because of down-regulation of Fe sequestration by
DMT-1. The authors suggested that decreased lung clearance of Fe may lead to pro-
duction of ROS and may enhance the growth of pathogens in lung tissue.
ʼ
M Fe or 10
ʼ
Critical Comments on In Vivo Studies with Individual Metals
The studies we reviewed in this section focus on Fe, Ni and V and are a logical
extension of the studies conducted with ROFA. In general, the studies were appro-
priately designed and executed. Although the studies confi rm that these three metals
induce infl ammatory and cardiac effects at high doses, we have the same concerns
regarding relevance to actual human exposures as with the ROFA studies.
Specifi cally, the exposure levels were much higher than ambient exposure levels,
and humans are exposed to mixtures rather than to individual components of the
mixtures.
Summary Comments on In Vivo Studies
With few exceptions (noted in the individual reviews), the laboratory animal studies
summarized in this paper were generally well-designed, followed similar protocols
and used appropriate statistical methods (including post-hoc corrections for multi-
ple comparisons), and measured responses relevant to respiratory tract infl amma-
tion. The majority of the
in vivo
studies used a limited number of well-characterized
particulate sources, archived PM from the Utah Valley during the years referenced
in the studies by Pope, and a number of study authors used ROFA from specifi c
power plants. In summary, the results of the
in vivo
studies that we reviewed were
supportive of the hypothesis that PM metals play a causal role in the respiratory and
cardiovascular morbidity and mortality reported in the epidemiologic literature.
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