SCREENING FOR GENETIC PREDISPOSITION TO MUTAGENS IN CANCER-PATIENTS

Both genetic and environmental factors are known to play an important role in the development of cancer. To determine whether, among individ uals who develop cancers, some may have been more susceptible to the m utagenic effects of environmental agents, skin biopsies were taken fro m 79 cancer patients with different common types of cancers (e.g., lun g, breast, bladder, colon, cervix, ovary, brain, vocal cord, uterus, s kin, testis, stomach, basal cell carcinoma, leukemia, etc.). Fibroblas t cultures have been established from skin explants from nearly all of the patients. The sensitivity of some of these cells as well as a num ber of other fibroblast strains established from ''clinically normal'' individuals to a battery of mutagenic agents (e.g., ethylmethane sulf onate, methylmethane sulfonate, ethidium bromide, actinomycin D, mitom ycin C, bleomycin, camptothecin), which induce different kinds of DNA damage was examined. For the control group of fibroblasts, a normal ra nge 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 differe nces in sensitivity were observed for ethidium bromide. The fibroblast strains established from fetal tissue were found to be highly resista nt to ethidium bromide, whereas fibroblasts from two clinically normal persons exhibited greatly enhanced sensitivity to this agent. The gen etic or biochemical basis of increased sensitivity or resistance to et hidium bromide remains to be determined. The sensitivity of cells from 28 cancer patients to a number of the mutagenic agents was also exami ned. Most of these strains exhibited normal range of sensitivity to th e mutagens; however, a few showed small but noticeable differences in sensitivity to specific agents. The fibroblast strains from cancer pat ients provide a useful resource to examine the genetic and metabolic f actors that may be important determinants in cancer susceptibility.