misshapen sperm and variability in DNA content, These experiments demonstrate for the first time the potential utility of sperm DNA measurements to monitor for chemical and physical genetic toxins in mammals including man. Fifty men who worked in a pesticide production plant with carbaryl were shown to have more semen defects than men ina new-hire control group. In addition, cancer chemotherapeutic drugs were shown to induce sperm defects. Sperm morphology and counts were found to be sensitive indicators of chemical exposure. ‘These studies are part of the validation phaseto determine whether sperm defects in man can be used to quantitate chemical exposure. Considerable mutagen detectable with a bacterial assay is formed during the grilling of ground beef to a well-done, but non-charred state. This mutagen appears to be formed from free amino acids of fragments of protein molecules and not from intact protein. However, preliminary results with mammalian bioassays indicate much smaller effects of the mutagen in higher organisms. These studies will allow estimation of potential hazard to the population from common cooking processes and design of preventive measures | based on thorough knowledge of mechanisms. Activation with specifically induced rodent metabolizing liver enzymes (cytochrome P-450's) was found necessary for cooked beef extracts to cause bacterial mutations. Best induction was with PCB's, a common terrestrial and aquatic pollutant, and polycyclic aromatic hydrocarbons, common to cigarette smoke, barbecued foods and polluted air. The induction specificity of the liver enzymes has been used to help identify the active compounds in cooked beef extracts. Mutagen-activating enzymes from the intestine were also increased by the inducers and natural flavones, common in the human diet, gave the biggest effect. Since the frequency of human cancer of the G.I. tract is rising and man does ingest both cooked beef and the flavones, it is plausible that activation needed for mutagenicity/carcinogenicity could occur in the human intestine. A flow cytometric method for measuring the cell cycle kinetic properties of the stem cells of the intestinal epithelium was developed. This will allow study of the response of these cells to chemotherapuetic agents and theminimization of damage to this important normal tissue during cancer chemotherapy. Groups of rats are being induced to develop bladder cancer slowly over a year's period. Cancer cells at many stages in heoplastic transformation are obtained by surgically removing the lesions from the appropriate rat. This is an excellent model for studying the cell biology of neoplastic transformation, and for research on early diagnosis of bladder cancer in humans. 5010106