Tsien Delivers Falk Lecture

1993 Falk Memorial Lecture. (left to right) Lecture coordinator Elizabeth Murphy; lecturer Roger Y. Tsien; Director Kenneth Olden; Falk's widow, Gabrielle Falk; Falk's son, Donald H. Falk; and Falk's sister, Eva Wulkan. account for only 15% of all colorectal cancers, it is likely that both inheritance and environmental factors play important roles in the pathogenesis of this disease. Scientists at NIEHS organized an interactive workshop last fall among researchers in environmental carcinogenesis and those studying the molecular biology of colorectal cancer to examine potential interactions between environmental factors and molecular genetics in this cancer. At the workshop, June Dunnick, one of the workshop organizers, with Dale Sander and Ronald Melnick and NIEHS colleague Michael R. Elwell, reviewed studies done within the Department of Health and Human Services primarily at NIEHS as a part of the National Toxicology Program. Of 435 chemicals tested in long-term rodent studies by National Cancer Institute, and later by NTP, 14 have shown some evidence for colorectal cancer in the rat. Colorectal cancer is rarely found as a spontaneous tumor in these rodent models, occurring in the historical database at an incidence of less than 0.1%. Future research will include studies to characterize the spectrum of genetic changes in colorectal cancers induced by bromodichloromethane and other brominated chemicals. Dunnick noted, "Further research on the metabolism of brominated chemicals is needed to identify specific enzyme systems involved." She said that studies are being conducted by Robert Langenbach at NIEHS using isolated cell cultures with specific P450 isozymes to identify P450dependent mutational changes caused by brominated chemicals that may reflect early genetic events in the multistep carcinogenic process. Epidemiologists at the workshop recommended that epidemiology studies be expanded to geographic areas where there are high exposures to trihalomethanes and to other sources of exposure to brominated chemicals. Melnick stated that interrelating the findings from toxicology, epidemiology, and molecular biology studies will help elucidate the contribution of environmental factors in colorectal cancer.