Screening for genetic predisposition to mutagens in cancer patients
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abstract
Both genetic and environmental factors are known to play an important role in the development of cancer. To determine whether, among individuals who develop cancers, some may have been more susceptible to the mutagenic effects of environmental agents, skin biopsies were taken from 79 cancer patients with different common types of cancers (e.g., lung, breast, bladder, colon, cervix, ovary, brain, vocal cord, uterus, skin, testis, stomach, basal cell carcinoma, leukemia, etc.). Fibroblast cultures have been established from skin explants from nearly all of the patients. The sensitivity of some of these cells as well as a number of other fibroblast strains established from "clinically normal" individuals to a battery of mutagenic agents (e.g., ethylmethane sulfonate, methylmethane sulfonate, ethidium bromide, actinomycin D, mitomycin C, bleomycin, camptothecin), which induce different kinds of DNA damage was examined. For the control group of fibroblasts, a normal range of toxicity for all of the above agents have been established. In contrast to other mutagens for which sensitivity of all of the control cell strains lay within a narrow range, large and interesting differences in sensitivity were observed for ethidium bromide. The fibroblast strains established from fetal tissue were found to be highly resistant to ethidium bromide, whereas fibroblasts from two clinically normal persons exhibited greatly enhanced sensitivity to this agent. The genetic or biochemical basis of increased sensitivity or resistance to ethidium bromide remains to be determined. The sensitivity of cells from 28 cancer patients to a number of the mutagenic agents was also examined. Most of these strains exhibited normal range of sensitivity to the mutagens; however, a few showed small but noticeable differences in sensitivity to specific agents. The fibroblast strains from cancer patients provide a useful resource to examine the genetic and metabolic factors that may be important determinants in cancer susceptibility.
