URI researcher deciphers how lead affects brain

KINGSTON, R.I. -- September 6, 2000 -- According to the Centers for Disease Control, exposure to lead is the number one environmental hazard facing children in America and the sixth leading cause of emergency room visits by children under age 6. While scientists generally agree that early exposure to lead lowers I.Q. levels by 5 to 10 points and results in learning disabilities and hyperactivity, they don't know how or why such problems occur.

But a University of Rhode Island toxicologist may have just found the key.

Research conducted by Warwick resident Nasser H. Zawia, associate professor of biomedical sciences in URI's College of Pharmacy, has shown that low concentrations of lead interferes with the regulators of genes important for growth in the brain.

"When a child's brain is developing, a family of proteins keeps a schedule of gene expression, like the script of a play, so that the necessary interactions between gene products happen at the right time," explained Zawia. "If children are exposed to lead during these critical windows of neural development ­ up to age 2 ­ their brains become damaged and they are cognitively deficient for the rest of their lives."

Zawia likens the family of proteins to "switch operators" that tell the brain's 100 billion interconnected cells when to grow and interact with other cells. "Lead causes this switching to happen in an uncoordinated manner, which results in less than optimal wiring of the brain," he said.

Children become exposed to lead in a variety of ways, including from lead-based paint chips in old houses and water from old plumbing pipes soldered with lead. These low-level chronic exposures from multiple sources of lead are a significant hazard.

Zawia has investigated the physiological effects of lead by studying both individual brain cells and entire animals.

By introducing minute amounts of lead into the drinking water of pregnant rats and comparing the developing brains of their offspring to brains of unexposed rats, Zawia observed the subtle effects of low-level lead exposure and analyzed the amount of lead found in the animals' blood and tissues.

At the same time, Zawia and his associates introduced lead to cultured brain cells to assess how individual cells are affected. They found that the structure, biochemistry and multiplication of these cells changed as a result of the lead.

"Low levels of lead appear to act like a growth factor, displacing or disturbing zinc proteins in the nucleus of the cells and changing their structure so they are no longer suitable to binding DNA," Zawia said. "If these proteins can't bind DNA, they can't perform their switching role."

Funding for this research was provided by the National Institute for Environmental Health Sciences.

Zawia said that even though lead was removed from paint and gasoline many years ago, more than a million children in the U.S. have lead levels in their blood that is considered unsafe. He recommends increased efforts at prevention, education, regulation and early detection to minimize future risks.

"Now that we know the proteins that are affected by lead, scientists can begin to think about how to prevent it and strategies for treatment."

For Information: Nasser Zawia 401-874-5909, Todd McLeish 401-874-7892