Mortimer L. Mendelsohn

Case-control study of malignant melanoma among employees of the Lawrence Livermore National Laboratory

During 1972 to 1977, the Lawrence Livermore National Laboratory (LLNL) experienced increased diagnosis of malignant melanoma among employees. In 1984, a report on the results of a case-control study of 39 cases concluded that occupational factors, including exposures to ionizing radiation and to chemicals, caused the excess incidence. The study reported here, based on results from 69 case-control pairs, re-examines the role of the occupational factors implicated by the earlier study in melanoma causation. Results from this study suggest that constitutional factors, including skin reactivity to sunlight, sunbathing frequency, and number of moles, explain most of the excess melanoma. Exposures to occupational factors, including ionizing radiation and chemicals, were found to be no different in cases than in controls.

Focus-Assist Device for a Flying-Spot Microscope

Uncertainty in locating optimum focus can be a major problem when a scanning microscope is used as an input to a quantitative image-analysis system. Our novel solution to this problem is to maximize the integral of the video light-loss signal above a threshold, when the threshold is arbitrarily set above background and within the range of grayness of the image. This algorithm has been incorporated into a real-time analog device to monitor the quality of focus. The focus-assist device uses IC operational amplifiers and has a bandpass of 0.5 MHz. When the device is used with images of metaphase chromosomes, the standard deviation of optimum focus is reduced to 0.09 ?m as contrasted to the unassisted value of 0.37 ?m. The device is simple, fast, reliable, and extremely sensitive. It should have general application to both macro- and microscopic scanning systems.

Antimutagenic effects in humans

The application of antimutagenicity studies to human somatic mutation is discussed, with emphasis on the potential for future studies. Five assay-gene combinations are now available for measuring human somatic mutation in lymphocytes and erythrocytes. Results with these combinations have defined the human background levels, and show clear responses of mutant frequency to a variety of mutagens. The testing of antimutagenic effects on background frequencies is feasible, but has not yet been done. The major uncertainty in such studies is the unknown age of mutant cells in the background, since only the newly forming mutants are potentially susceptible to most antimutagenic treatments. Intervention studies in the face of active mutagenicity and the use of other genotoxicity endpoints, such as chromosome aberrations, micronuclei and DNA adducts, are considered briefly.

Optimization of radiotherapy

Abstract Carcinoma of the nasal pharynx, Spinal cord, Optimization of therapy, Treatment characteristic (TC), Radiotherapeutic operating characteristic (ROC).

Extrapolation of Mutagenicity Testing to the Human

Agricultural genetic toxicology is typical of the challenging problems now being encountered in the rapidly growing field of environmental mutagenesis. Both fields involve a rich diversity of important chemicals, some already known mutagens, a few known carcinogens; both have some hints of human toxicity, but by and large no concrete human data; and both are floundering in the scientific and legal definition of human risk, as well as in regulatory confusion over when and to what degree to control.

PROSPECTS FOR CELLULAR MUTATIONAL ASSAYS IN HUMAN POPULATIONS

Practical, sensitive, effective, human cellular assays for detecting somatic and germinal mutations would have great value in environmental mutagenesis and carcinogenesis. When available, such assays should allow us to fill the void between human mutagenicity and the data that exist from short-term tests and from mutagenicity in other species. We will be able to validate the role of somatic mutation in carcinogenesis, to identify environmental factors that affect human germ cells, to integrate the effects of complex mixtures and the environment in the human subject, and to identify people who are hypersusceptible to genetic injury. Human cellular mutational assays, particularly when combined with cytogenetic and heritable mutational tests, promise to play pivotal roles in estimating the risk from low-dose radiation and chemical exposures. These combined methods avoid extrapolations of dose and from species to species, and may be sensitive enough and credible enough to permit politically, socially and scientifically acceptable risk management.