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Biomedical subjects

M L Mendelsohn

Publications and source records attributed to M L Mendelsohn.

At least 19 recordsLinked to original sources
PubMed2001

Evaluation of three somatic genetic biomarkers as indicators of low dose radiation effects in clean-up workers of the Chernobyl nuclear reactor accident.

The goals of this study were to assess three biomarkers of genetic effect for their individual and collective ability to detect and estimate radiation exposure in Russian Chernobyl clean-up workers. Work assignments were planned to limit dose to 0.25 Gy. The three biomarkers employed were chromosome translocations detectcd in lynmphocytes by florescence in situ hybridisation (FISH), and mutation at two genes, glycophorin A (GPA) in red blood cells detected by flow cytometry and hypoxanthine phosphoribosyltransferase (HPRT) in lymphocytes detected by selective cell culture. Samples were Obtained from 1992 to 2000. The time between exposure at Chernobyl and sample acquisition was > or =5 years. The lymphocyte assays detected an elevation over controls in average outcomes it clean-up workers: translocation rates were 46% higher when adjusted for age and smoking and HPRT mutant frequencies were were 16% higher when adjusted for age. The G PA assay did not detect an exposure effect. The results indicate that measuring frequency of translocations by FISH is preferred for low dose radiation, retrospective biochemistry.

Adult↗
PubMed1999

A model for radiation-related cancer suggested by atomic bomb survivor data.

The age-time patterns of excess cancer risk among A-bomb survivors followed up by the Radiation Effects Research Foundation inevitably carry implications regarding the mechanisms of radiation-related cancer. It has recently been found, quite surprisingly and in contrast to impressions given by the relative risks, that for most solid cancers the excess incidence rates themselves depend very little on age at exposure or time since exposure, but mainly on attained age. This paper investigates a mechanistic model that conforms to these age-time patterns. The essence of the model, which is highly idealized, is that: (a) a cancer is caused by mutations that accumulate in a stem cell throughout life, essentially the Armitage-Doll multistage model, and (b) radiation is a general mutagen that can cause virtually any of these mutations. Although postulate (b) departs from previous modeling considerations, the extent to which it explains various aspects of the data in substantial detail is remarkable. A strength of the model is that, similarly to the Armitage-Doll multistage model but differently from many others, it predicts characteristic age-time patterns of excess rates rather independently of its parameter values. The consequence of (a) is that, in Armitage-Doll fashion, background rates increase throughout life as a power of age. The consequence of (b) is that excess absolute rates do not depend on age at exposure and increase with age to a power one less than that of the background rates. Thus the excess relative risk, which is the ratio of these rates, decreases throughout life as 1/age with no dependence on age at exposure. Although this age pattern of relative risks corresponds closely to the RERF data for solid cancer, the interpretation of such a description is quite different from the usual one in which age at exposure plays a primary role.

Adult↗
PubMed1997

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.

Algorithms↗
PubMed1992

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.

Antimutagenic Agents↗
PubMed1990

New approaches for biological monitoring of radiation workers.

Methods for measuring somatic mutation and chromosome aberration in humans are currently advancing and provide important new opportunities for biologic dosimetry of nuclear workers. Methods to test somatic mutation in four human genes (hprt, hla-a, glycophorin A, and beta globin) are reviewed briefly and evaluated for their applicability to biological radiation dosimetry of nuclear workers. Two somatic mutation tests can be currently recommended: an HPRT method applied to recently exposed workers and the glycophorin A method applied to workers exposed over their working lifetime. A new method of chromosome analysis using DNA hybridization with chromosome-specific gene libraries allows one to paint single or multiple chromosome pairs in standard metaphase preparations. This method is ideal for rapid and reliable detection of reciprocal translocations, the key lesion for the evaluation of long-term radiation exposure. Both mutational and aberrational approaches should be fostered in the expectation that they will complement other forms of dosimetry and will improve our ability to clarify whether or not significant health effects are dosimetrically related.

Chromosome Aberrations↗
PubMed1989

Potential DNA methods for measuring the human heritable mutation rate.

Potential methods are reviewed for estimating human heritable mutation rates by comparing the DNA of parents of offspring. In the 4 years since the Alta Workshop on this subject, information has accumulated on several of the six methods detailed in that meeting. Some of the methods now appear to be infeasible, and all continue to be too inefficient for practical implementation. Newer DNA approaches are discussed, including several that could become practical enough for implementation. Finally, DNA-oriented methods using human sperm are considered as possible alternatives to the heritable approaches.

Base Sequence↗
PubMed1987

Biomarkers in the detection of human heritable and germinal mutagenesis.

An important potential use of biomarkers in human toxicology is the detection of induced mutational events in offspring and germ cells of exposed individuals. The importance, of course, is in risk estimation and the identification and prevention of exposure conditions that are harmful to the human genome. The challenge is to discover methods of sufficient power to find the rare, random, mutational events and to discriminate such events from other sources of molecular variation. Finding mutations is essentially a search for disorder. Normal biomarkers are inherently unsuitable in a positive search for disorder; instead one must either use abnormal markers or be prepared to search negatively, i.e., to look for and somehow validate the rare absence of a normal marker. In spite of these difficulties, there is progress to report and hope of future success in this field.

DNA, Recombinant↗