In a new study, environmental
pollutants found in fish were shown to obstruct the human body's natural
defense system to expel harmful toxins. The Scripps Institution of
Oceanography at UC San Diego-led research team suggests that this
information should be used to better assess the human health risks from
eating contaminated seafood. The study was published in the April 15
issue of the journal Science Advances.
A protein found in cells of nearly all plants and animals,
called P-gp, acts as the cell's bouncer by expelling foreign chemicals
from the body. P-gp is well known for its ability to transport
therapeutic drugs out of cancer cells and, in some cases, rendering
these cells resistant to multiple drugs at once.
To determine how effective P-gp is at ridding cells of industrial and agricultural pollutants found in seafood, collectively known as persistent organic pollutants
(POPs), the Scripps research team conducted a biochemical analysis of
P-gp proteins from humans and mice against POPs. The scientists focused
on POPs most commonly found in human blood and urine, and also detected
in the muscle tissues of wild-caught yellowfin tuna. The pollutants
included older "legacy" compounds such as the pesticide DDT as well as
newer industrial chemicals, such as flame retardants.
Working with researchers at UC San Diego's Skaggs School of
Pharmacy and Pharmaceutical Science and School of Medicine, the
researchers discovered that all 10 pollutants interfered with the
ability of P-gp to protect cells. The study was also the first to show
how one of the 10 pollutants, PBDE-100, commonly used as a flame
retardant in upholstery foam and plastics, binds to the transporter
protein. The POP binds to the protein in a similar way as
chemotherapeutics and other drugs, but instead of being transported out
of the cell, the bound POP ultimately inhibits the protein's ability to
perform its defense function.
"When we eat contaminated fish, we could be reducing the effectiveness of this critical defense system
in our bodies," said Amro Hamdoun, an associate professor in the Marine
Biology Research Division at Scripps, and lead author of the study.
The researchers point out that newborns and fish larvae are
two of the most vulnerable populations. Newborns are particularly
vulnerable since they are exposed to high concentrations of POPs in
breast milk, and have low amounts of the protective P-gp protein. Fish
larvae may be at increased risk since the accumulation of pollutants may
slow down the animal's defense system to combat other marine
pollutants, such as oil hydrocarbons encountered at oil spill sites.
"We show that these inhibitors are found in the fish we eat," said
Scripps postdoctoral researcher Sascha Nicklisch, an author of the
study.
The Scripps researchers suggest that environmental chemicals
should be tested to determine if they impede the effectiveness of the
body's natural defense system to expel these, and other foreign
chemicals. The U.S. Food and Drug Administration currently recommends
similar testing on pharmaceuticals.
"Its unsettling to find that all of the tested persistent environmental pollutants
interfered with the P-gp protein's ability to protect cells," said
Jacob James, managing director of the Waitt Foundation, who funded the
study. "Even more troubling are the results showing that PBDE-100 binds
to the P-gp protein, in essence latching onto and poisoning the
'bouncer' whose job it is to throw out the toxins. We can assume that
some 'hot' fish carry more than one toxin and that seems like a credible
triple threat, as the results with mixtures suggest that multiple
toxins do act as 'force multipliers' in degrading cells ability to
respond. We are the only species that can influence entire food chains
and habitats, we must act more responsibly in the design and use of
chemicals in our environment as well as work on economically feasible
ways to measure and understand the impacts of those chemicals in
seafood, and ourselves."
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