According to study, chemotherapy may increase illness susceptibility in future generations

According to study done by Washington State University, a popular chemotherapy treatment may pass on a hazardous legacy to children and grandchildren of teenage cancer survivors. The study, published online in iScience, discovered that male rats given ifosfamide during adolescence produced offspring and grand-offspring with an elevated risk of illness. While past studies have demonstrated that cancer treatments can raise a patient’s risk of having the disease later in life, this is one of the first studies to indicate that vulnerability can be transmitted down to the third generation of unexposed kids.

“The findings suggest that if a patient receives chemotherapy, and then later has children, that their grandchildren, and even great-grandchildren, may have an increased disease susceptibility due to their ancestors’ chemotherapy exposure,” said Michael Skinner, a WSU biologist and corresponding author on the study.

Skinner stressed that the findings should not deter cancer patients from undergoing chemotherapy because it may be a very successful treatment. Chemotherapy medications target malignant cells and inhibit their replication, but they have numerous adverse effects since they affect the entire body, including the reproductive system.

Given the consequences of this study, the researchers advise cancer patients who wish to have children later to take safeguards, such as freezing sperm or ova before undergoing chemotherapy.
Researchers subjected a group of young male rats to ifosfamide for three days, simulating the length of treatment that a teenage human cancer patient may get. These rats were then mated with female rats that had not been exposed to the medication.

The pups were then mated with another group of unexposed rats. Although the first-generation kids had some exposure to the chemotherapy medication since their fathers’ sperm was exposed, researchers discovered a higher incidence of illness in not just the first-generation, but also the second-generation, who had no direct contact to the drug. While there were some generational and gender variances, the related concerns included a higher prevalence of renal and testicular disorders, as well as delayed puberty and abnormally low anxiety, indicating a diminished capacity to detect danger. The researchers also looked at the rats’ epigenomes, which are biological processes that are unrelated to DNA sequence but impact gene expression, such as turning genes on or off.

Previous study has demonstrated that toxicant exposure, especially during development, can result in epigenetic alterations that are passed down through sperm and ova. The findings of the researchers’ investigation revealed epigenetic alterations in two generations of rats subjected to chemotherapy. The fact that these abnormalities were observed in grand children who had no direct contact to the chemotherapy treatment suggests that the harmful effects were passed down through epigenetic inheritance.

Skinner and colleagues at the Seattle Children’s Research Institute are presently doing a human research with former teenage cancer patients to understand more about the impact of chemotherapy on fertility and illness susceptibility later in life.

A better knowledge of chemotherapy’s epigenetic shifts could also help inform patients of their likelihood of developing certain diseases, creating the possibility of earlier prevention and treatment strategies, Skinner said.
“We could potentially determine if a person’s exposure had these epigenetic shifts that could direct what diseases they’re going to develop, and what they’re going to potentially pass on to their grandchildren,” he said. “We could use epigenetics to help diagnose whether they’re going to have a susceptibility to disease.”