PubMed HealthSearch

Biomedical subjects

M L Mendelsohn

Publications and source records attributed to M L Mendelsohn.

At least 19 recordsLinked to original sources

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

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

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

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

Hydrodynamic orientation of sperm heads for flow cytometry.

Two specially shaped sample injection tubes orient flat-shaped mature sperm heads in a flow cytometer. Orientation allows control of a photometric difficulty experienced with some flow cytometers in the measurement of fluorescent and scattered light from sperm and other flat cells. Both relative DNA-stain content and a measure of cell flatness can now be determined simultaneously for each cell at the high rates possible with flow instruments.

Animals