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Radiation Exposure Study in Mice Hints at Cause for Testicular Cancer

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The incidence of testicular cancer has increased steadily in recent years, but the cause has been elusive. MD Anderson Cancer Center scientists published research in mice Monday indicating that DNA-damaging agents might be the culprits.

Male fetuses of mothers exposed to radiation during early pregnancy had an increased chance of developing testicular cancer, according to their article in the online journal PLoS ONE.

The study is the first to find an environmental cause for testicular germ cell tumors. "This discovery launches a major shift in the current research model, placing DNA-damaging agents in the forefront as likely mediators of testicular cancer induction," said corresponding author Gunapala Shetty, Ph.D., assistant professor in MD Anderson's Department of Experimental Radiation Oncology.

During the past 50 years, the incidence of testicular cancer has tripled in young Caucasian men throughout the world.  The American Cancer Society reports more than 8,500 new cases of testicular cancer are diagnosed each year in the United States.

"This increase and the characteristics of germ cell tumors strongly suggest that fetal exposure to an environmental agent is responsible," Shetty said. "However, the identification of any agent producing increases in testicular cancer has eluded scientists."

Endocrine disruptors, chemicals that alter the endocrine -- or hormonal -- system, have been widely suggested as the cause of testicular cancer. The researchers separately tested two such substances, the estrogen diethylstilbestrol (DES) and the anti-androgen flutamide, but neither caused cancer to increase in a mouse strain with a high spontaneous incidence of testicular cancer.

When researchers gave modest doses of radiation, which is a DNA-damaging agent, to female mice in the middle of their pregnancies, all  the male offspring developed testicular cancer, compared to 45 percent of mice not exposed to radiation.  And the tumors were more aggressive and had more sites of origin.

"Although radiation exposure of pregnant females has been declining and is unlikely to be responsible for this increase, we intend to follow this up with studies of DNA-damaging chemicals found in cigarette smoke and air pollution, to which exposures of pregnant women have been increasing," said study senior author Marvin Meistrich, Ph.D., professor in Experimental Radiation Oncology.
 
Additional information
MD Anderson news release

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