Common herbicide disrupts human hormone activity

Atrazine affects the endocrine systems of zebrafish at levels lower than U.S. drinking-water standards‚ and impacts human cells in tissue cultures.

The second most widely used herbicide in the U.S. could cause serious problems for both fish and humans, according to new research. In a paper published May 7 in PLoS ONE (DOI 10.1371/journal.pone.0002117 ), scientists from the University of California San Francisco examined atrazine’s endocrine-disrupting effects in zebrafish, a commonly used laboratory animal. In parallel studies of cultured human cells, the researchers found indications that some human genes may be more sensitive to atrazine than previously thought.

The team subjected cells and live zebrafish to environmentally relevant doses of atrazine. Fish in the lab had slightly higher female-to-male ratios than populations not exposed to atrazine, indicating some feminization induced by the weed killer.

More clear, however, was the elevated activity of a gene that encodes aromatase, which is linked to estrogen production. Zebrafish have two aromatase genes, one regulated by estrogen and the other by both estrogen and a receptor called NR5A. The researchers found that environmentally relevant concentrations of atrazine increased aromatase expression by activating NR5A receptors. The experiments show definite effects at 2 parts per billion (ppb); the U.S. EPA has set drinking-water limits for humans at 3 ppb for atrazine. The pesticide is currently under review. The researchers also found that atrazine activated NR5A receptors in human cell lines, affecting other genes that are critical to steroid synthesis and development.

“The zebrafish model made it easier to tease out the potential mechanisms,” says John Incardona, a research toxicologist for the National Oceanic and Atmospheric Administration (NOAA) Northwest Fisheries Science Center. “They still don’t have the exact mechanism,” he adds, but the results are a “big step forward in identifying the mechanism of action of atrazine in producing these endocrine effects.”

“Freshwater fish like zebrafish are going to be very sensitive to this” herbicide in the environment, says Holly Ingraham, coauthor of the new research. Although the debate about atrazine’s environmental impacts has focused on Xenopus frogs, the lab animals may not be the best genetic model organism for understanding wild frog populations and may metabolize the chemical differently.

“The human data provide a brand new framework to look at atrazine,” Ingraham continues. Future work should examine other genes, she says, because they may be much more sensitive to atrazine and could be linked to other important systems, such as reproduction and adrenal gland function. NAOMI LUBICK