Future research directions to study genetic damage in germ cells and estimate genetic risk.
Open Access
- 1 May 1996
- journal article
- review article
- Published by Environmental Health Perspectives in Environmental Health Perspectives
- Vol. 104 (suppl 3) , 619-624
- https://doi.org/10.1289/ehp.96104s3619
Abstract
The late Frits Sobels developed a parallelogram model to estimate genetic risk to humans based on experimental data in somatic cells (peripheral blood) of exposed animals and humans and on data from progeny studies of exposed animals (mice). Recently, an extension to the original parallelogram model was proposed to bridge the gap of extrapolation between rodent and human germ cells by studying sperm samples. The comparison in the parallelogram of rodent/human sperm data with data from rodent progeny tests to derive at an estimate of human progeny at risk is more promising. Therefore, data on all possible end points, DNA adducts, mutations, chromosomal aberrations, and aneuploidy, should be obtained in sperm of exposed rodents and humans. The technology from somatic cell studies is available or adaptable to sperm studies. Sperm samples lend themselves to automated analyses because they are a homogeneous cell population. By flow cytometry or image analysis, large cell samples can be studied per individual. Animal experiments could be conducted in the actual range of chronic human exposure to low doses. The acceptability of extrapolation from the high acute doses so far used in animal experiments to low chronic doses of human exposure could be assessed. Proof could be obtained in human germ cells for the assumption that data from animal experiments can be extrapolated to humans. Data from transgenic rodent systems may play an important role in the extension of the parallelogram approach to genetic risk estimation by providing a link between cancer and genetic risk estimates.Keywords
This publication has 43 references indexed in Scilit:
- Lessons learned from epidemiologic studies of environmental exposure and genetic diseaseEnvironmental and Molecular Mutagenesis, 1995
- Population genetics of induced mutationsEnvironmental and Molecular Mutagenesis, 1995
- Detection of chemical mutagens using Muta® Mouse: a transgenic mouse modelMutagenesis, 1993
- A dose-response analysis of ethylnitrosourea-induced recessive specific-locus mutations in treated spermatogonia of the mouseMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1990
- Models and assumptions underlying genetic risk assessmentMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1989
- Enzyme-activity mutations detected in mice after paternal fractionated irradiationMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1986
- Induction of gene mutations in mice: The multiple endpoint approachMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1985
- Mutation-rate determinations based on electrophoretic analysis of laboratory miceMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1981
- Dominant cataract mutations induced by γ-irradiation of male miceMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1979
- Mutation rates at a new set of specific loci in the mouseGenetics Research, 1966