Hunting for clues to the causes of cancer
Experimental findings by Berkley Lab cell biologist Mary Helen Barcellos-Hoff and her research group showed that exposure to ionizing radiation creates a microenvironment in the tissue that surrounds breast cells, which can cause even nonirradiated cells and their progeny to become cancerous. The discovery that it is the tissue surrounding breast cells that may be the primary target of ionizing radiation damage rather than the DNA within the cells suggests new and possibly more effective means of treating breast cancer.
“Repairing damaged tissue would be a much less cumbersome strategy for interrupting the cancer process than trying to repair individual damaged cells,” says Barcellos-Hoff. “We find that radiation elicits rapid and persistent global alterations in the mammary gland microenvironment. These radiation-induced microenvironments might lead to changes in the phenotypes (physical characteristics) of cells and their progeny that promote carcinogenesis.”
In one study, a special line of nonirradiated, nonmalignant breast cells were transplanted into mammary glands that had been exposed to low dosages (less than 5 grays or 500 rads) of ionizing radiation. Nearly 75 percent of these transplanted cells developed tumors and the effect persisted up to 14 days after the radiation exposure. Tumors did not develop when the same type of cells were transplanted into nonirradiated portions of the mammary glands.
Barcellos-Hoff and her research team established that damage to the irradiated tissue was generating signals that altered how the genomes of the transplanted cells were being expressed. This resulted in the creation of a new cell phenotype with physical characteristics that were cued by the extracellular signals to act cancerous. Breast cells acquiring the new phenotypes passed these characteristics on to their daughter cells.
“Genomes are like the keys on a piano, in that the same keys can be used to play a wide variety of music,” says Barcellos-Hoff.
“In our studies, the ionizing radiation elicited changes in how the genomes of the transplanted cells were being expressed by changing the extracellular signals they were receiving.”