A common chemotherapy drug may make future generations more susceptible to disease. The corresponding study was published in iScience.
Chemotherapy refers to drugs that treat cancer. There are several different types of chemotherapy drugs. In the current study, researchers investigated the effects of ifosfamide, an alkylating agent that prevents cells from reproducing by damaging their DNA. The drug is used to treat multiple varieties of cancer, including testicular cancer, bladder cancer, small cell lung cancer, cervical cancer, and ovarian cancer.
For the study, the researchers exposed young male rats to ifosfamide for three days to mimic a course of chemotherapy an adolescent human cancer patient may receive. They then bred these rats with female rats who had not been exposed to the drug. Their offspring were later bred with more unexposed rats.
The researchers noted that both offspring and ‘grand-offspring’ of treated mice experienced an increased likelihood of multiple conditions, including delayed or early pubertal onset, kidney disease, and testis disease. They noted that both male and female ‘grand-offspring’ also had lower levels of anxiety, indicating a lower ability to assess risk.
The researchers next analyzed the rats' epigenomes. Epigenetic changes do not change DNA, but change how the body reads DNA- including whether certain genes are switched on or off. They found that chemotherapy exposure resulted in epigenetic changes that lasted two generations.
The researchers are now studying former adolescent cancer patients to learn more about the effects of chemotherapy exposure on fertility and disease susceptibility later in life. Knowing more about how chemotherapy alters epigenomes could help clinicians inform patients of their risk of developing certain diseases, and make way for early prevention and treatment strategies.
The researchers noted that their findings should not dissuade cancer patients from taking chemotherapy as the treatments are nevertheless very effective for treating cancer. They also noted that their study was based on a rodent model and that it remains to be seen how chemotherapy affects epigenetics across human generations. They did note, however, that patients may wish to consider cryopreservation of egg cells and sperm cells prior to chemotherapy.