'Destruct' triggers may be jammed in tumor cells, UF geneticists say

Scientists first noticed drastic changes in sensitivity to radiation in developing fruit fly cells in the mid-1970s. Similarly, a sensitive-to-resistant transformation takes place in people during the development of brain cells, which are extremely sensitive to radiation in their formative stages but more durable once they grow into adult neurons.

However, the underlying cellular and molecular causes of the transformations were undetected. The latest findings suggest that like the fruit fly cells, tumor cells may have a degree of epigenetic protection from radiotherapy or chemotherapy.

“We are talking about a piece of DNA that is very sensitive when open, but modification of its supporting structure has caused it to condense,” said Zhou, who is affiliated with the UF Shands Cancer Center and the UF Genetics Institute. “If we reverse this and open the DNA supporting structure, we can conceivably make the cells sensitive to radiation once more. Controlling the blocking-unblocking mechanism to make the cells sensitive could potentially lead to better cancer therapy.”

Conceivably, certain drugs that open “enhancer” regions of cell-death genes in tumor cells could improve the effectiveness of cancer treatments.

“The scientists took a different approach to look at the regions of the genome important for DNA-damage induced cell death,” said Kristin White, Ph.D., an associate professor of dermatology at Harvard Medical School and Massachusetts General Hospital, who did not participate in the research. “One of the most interesting aspects of this work is the finding that changes in chromatin structure regulate the expression of genes that are important in this death, and that this regulation can extend over long distances in the genome.

“The research shows there is still a lot to learn about DNA damage-induced cell death,” she said. “We need to understand all aspects of this if we want to improve cancer therapy. This work suggests that we need to look harder at chromatin-modifying enzymes as new targets to alter the response of cancer cells to radiation.”

The research was supported by a National Institutes of Health grant.