Researchers identify genes affected by Methotrexate (MTX)

A Queen's University study of fruit flies that may revolutionize the way birth defects are studied has identified the genes affected by a widely-prescribed drug known to cause birth defects.

Methotrexate (MTX), a popular cancer-fighting drug also used to treat psoriasis, ectopic pregnancies, rheumatoid arthritis, and lupus, lasts a long time in the body and causes birth defects in children from women who have it in their systems. The study of the drug's effect on fruit flies has allowed Queen's researchers including graduate student Joslynn Affleck to identify the genes on which the drug acts.

"We hope that through this model system we can provide insight into mammalian birth defects, which may be expected to increase in frequency in the future, due to the recent elevated use of MTX," says Affleck.

Many of the genes found to be affected by MTX are involved in cell cycle regulation, signal transduction, transport, defense response, transcription, or various aspects of metabolism.

"This study shows that MTX treatment has multiple targets," says Affleck. "And this provides us with a novel invertebrate model for the study of drugs that cause birth defects." The findings, funded by NSERC, are set to be published by Toxicological Sciences in the New Year.

"This is not a journal in the habit of publishing insect studies," notes biologist Dr. Virginia Walker, who co-authored the study. "The neat thing about this work is that fruit flies treated with this drug show 'birth defects' that are hauntingly similar to birth defects in human babies. Babies have bent limbs, tufts of hair and bulging eyes and the fruit flies have bent legs (and wings), tufts of bristles and rough eyes."

While identifying this gene array is significant in its own right, the successful use of fruit flies in this kind of study is a revelation to the researchers who view it as an efficient model for the initial testing of "rescue" therapies to try to prevent birth defects. Scientists can study the effect of the drug on the genes of as many as three generations of fruit flies in a month using readily available scientific tools, speeding up study times while keeping costs low.

"It also adds to the growing list of roles fruit flies can take," says Walker. Fruit flies are already used as models for aging, neural disease and cancer.