The Toxicologist - Society of Toxicology

elative to their controls. ST-depression was observed in all DE-exposed SH rats,
but not WKY rats. In conclusion, the dobutamine stress test shows that rat strains
with compromised cardiovascular systems are prone to elevated HR and arrhythmic
events when compared to the healthy strain. A single exposure to a toxic air pollutant
may increase the risk of triggering cardiac arrhythmias during exercise-like
stress conditions. (This abstract does not reflect EPA policy)
609 COMBINED EFFECTS OF DIESEL EXHAUST
PARTICLES AND HIGH GLUCOSE ON MMP-2
EXPRESSION IN HUMAN MONOCYTES.
R. Wan 1 , Y. Mo 1 , S. Chien 2 , D. J. Tollerud 1 and Q. Zhang 1 . 1 Environmental and
Occupational Health Sciences, University of Louisville, Louisville, KY and 2 Surgery,
University of Louisville, Louisville, KY.
A number of epidemiological studies and animal experiments have shown that individuals
with preexisting diseases, such as asthma, chronic obstructive pulmonary
disease (COPD), diabetes mellitus (DM), and cardiovascular diseases are more susceptible
to particulate matter (PM)-related health problems. Macrophages are the
first line of defense against inhaled particles and play an important role in PM-induced
pulmonary and systemic inflammation and cardiac impairment.
Hyperglycemia has been shown to activate macrophages/monocytes to secrete metalloproteinases
which are involved in various hyperglycemia-induced cardiovascular
diseases. However, few studies have focused on the activation of MMPs and the tissue
inhibitors of MMPs (TIMPs) in macrophages/monocytes from DM subjects
with exposure to diesel exhaust particles (DEP), one of the important components
of PM, though several epidemiological studies have shown that people with DM
were especially sensitive to effects of PM on daily mortality and heart disease hospitalization.
In this study, we determined the combined effects of DEP with or without
high glucose on human monocytes U937. Our results showed that exposure of
U937 cells to DEP, high glucose or DEP with high glucose, at a non-toxic dose, induced
reactive oxygen species (ROS) generation, increased phosphorylation of p38
and Erk1/2, and MMP-2 expression. Further, exposure to DEPs with high glucose
caused significantly more ROS generation in U937 cells than those exposed to
DEP or high glucose alone. Our results also showed that there were combined effects,
including increased phosphorylation of p38 and Erk1/2 and upregulation of
MMP-2 expression when U937 cells exposed to DEP with high glucose. Our results
suggest that co-exposure to DEP and high glocuse causes synergistic injury to
monocytes.
This work was partly supported by ALA(RG-872-N), AHA(086576D), KSEF-
1686-RED-11, Health Effects Institute (4751-RFA-05-2/06-12), T32-ES011564.
610 DISORDERED PORPHYRIN METABOLISM AMONG
AUTISTIC CHILDREN IS NOT ASSOCIATED WITH
MERCURY EXPOSURE.
J. S. Woods 1 , S. E. Armel 1, 2 , D. Echeverria 1, 3 and N. J. Heyer 3 . 1 Environmental
and Occupational Health Sciences, University of Washington, Seattle, WA, 2 Veritox,
Inc., Redmond, WA and 3 Battelle Centers for Public Health Research and Evaluation,
Seattle, WA.
Increased urinary concentrations of pentacarboxyl-, precopro- and copro- porphyrins
are associated with prolonged mercury (Hg) exposure in adults, and comparable
increases have been attributed to Hg exposure in children with autism
(AU). We compared urinary porphyrin concentrations in 2-12 year old neurotypical
(NT) children (n = 59) and same age children with AU (n= 57) and examined
the association between porphyrin levels and past or current Hg exposure.
Caregivers provided information at enrollment regarding medical, dental and dietary
Hg exposures. Urine samples from all children were acquired for porphyrin,
creatinine and mercury analyses. We conducted logistic regression analysis to determine
if porphyrin levels were associated with increased risk of AU. Mean urinary
porphyrin concentrations are naturally high in young children and decline by as
much as 2.5-fold between ages 2 and 12 years. Elevated copro- (p