Male fetuses of mothers that are exposed to radiation during early pregnancy may have an increased chance of developing testicular cancer, according to a study in mice at The University of Texas MD Anderson Cancer Center.
The study is the first to find an environmental cause for testicular germ cell tumors, the most common cancer in young Caucasian men.
“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,” says Gunapala Shetty, PhD, assistant professor in MD Anderson’s Department of Experimental Radiation Oncology.
“This increase and the characteristics of germ cell tumors strongly suggest that fetal exposure to an environmental agent is responsible,” Shetty says. “However, the identification of any agent producing increases in testicular cancer has eluded scientists.”
Endocrine disruptors, chemicals that alter the endocrine system, have been widely suggested as the cause of testicular cancer, but there has been no proof. Fetuses are especially vulnerable to even small amounts of the substances, which are known to cause developmental and cognitive issues.
The study began as an examination of endocrine disruptors as a possible cause of testicular cancer. Researchers separately tested two such substances, the estrogen diethylstilbestrol (DES) and the antiandrogen 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. But the results showed no increase in testicular cancer.
When researchers gave modest doses of radiation to female mice in the middle of their pregnancies, all of the male offspring developed testicular cancer, compared to 45% of mice not exposed to radiation. In addition, the tumors were more aggressive and had more sites of origin.
The study suggests that DNA-damaging agents, rather than endocrine disruptors, should be examined 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,” says Marvin Meistrich, PhD, professor in MD Anderson’s Department of Experimental Radiation Oncology.
The study opens the door to possibilities for wide-ranging investigation, 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,” Shetty says. “Studies 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.”
The article was published in PLoS ONE.
Release Date: Feb. 13, 2012
Source: The University of Texas MD Anderson Cancer Center