Fetus Exposed to Radiation Has Increased Risk of Testicular Cancer

“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, PhD, assistant professor in the University of Texas MD Anderson Cancer Center’s (Houston, USA) department of experimental radiation oncology.

According to the American Cancer Society (Houston, TX, USA), more than 8,500 new instances of testicular cancer are diagnosed each year in the United States. During the past 50 years, the incidence has tripled in young Caucasian men worldwide. “This increase and the characteristics of germ cell tumors strongly suggest that fetal exposure to an environmental agent is responsible,” Dr. Shetty said. “However, the identification of any agent producing increases in testicular cancer has eluded scientists.”

Endocrine disruptors, compounds that alter the endocrine--or hormonal--system, have been widely believed to be the cause of testicular cancer, but there has been no evidence. Fetuses are particularly susceptible to even small amounts of the substances, which are known to cause developmental and cognitive issues.

This study started as an examination of endocrine disruptors as a possible cause of testicular cancer. Researchers separately tested two such compounds, the estrogen diethylstilbestrol (DES) and the anti-androgen flutamide. The endocrine disruptors were introduced into a mouse strain with a high spontaneous incidence of testicular cancer, which should make them more sensitive to cancer caused by environmental agents. However, the study’s findings revealed no increase in testicular cancer. However, when researchers gave small 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% of mice not exposed to radiation. Moreover, the tumors were more aggressive and had more sites of origin.

This study suggests that DNA-damaging agents, instead of endocrine disruptors, should be assessed as a factor in the increased prevalence of testicular cancer. “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, PhD, professor in MD Anderson’s department of experimental radiation oncology.

This study opens the way for wide-ranging study, and researchers agree much work remains to be done. “A second class of DNA-damaging agents that we intend to study is chemotherapy drugs like cyclophosphamide, which are used to treat pregnant women with breast cancer,” Dr. Shetty said. “Studies at MD Anderson of the children of these women did not show increases in birth or developmental defects. However, we need to test these agents in our animal model since testicular cancer usually does not appear until early adulthood.”

Related Links:
University of Texas MD Anderson Cancer Center