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Published on: July 29, 2019
Genetic toxicology: lessons from the past, directions for the future
1Department of Preventive Medicine, University of Texas Medical Branch, Galveston 77555-1010.
Abstract:
Twenty-five years after the founding of the Environmental Mutagen Society, the need to detect germinal cell mutagens remains an unfulfilled goal. Instead we embarked upon a journey to characterize carcinogens by detecting mutations in nonmammalian or in vitro assays. Genetic toxicologists, in an attempt to devise a quick efficient strategy for detecting chemical carcinogens, committed two basic errors. The first error set us off on a 25-year quest for the definitive short-term assay for characterizing carcinogens; the second error, derived from the first, was to focus our efforts mostly toward determining effects in somatic cells rather than also looking for chemically induced effects in germinal cells. The time is now at hand to reestablish the credibility of the field of genetic toxicology and achieve the goals of the initial founders of the society. Having realized the shortcomings of nonmammalian studies, we should devote our efforts to developing suitable germinal cell assays in animals and where possible in humans. In addition to identifying germinal cell mutagens, we should also expand our efforts to evaluate chronic low-level exposures of human populations to potential cancer causing agents, using the rapidly developing methods of genetic biomonitoring.
Insights
Genetic toxicology research has focused on somatic cells, neglecting germinal cell mutagen detection for 25 years. Future efforts should prioritize developing germinal cell assays and biomonitoring for human exposure to carcinogens.
Area of Science:
- Genetic Toxicology
- Carcinogenesis Research
- Environmental Health
Background:
- The Environmental Mutagen Society was founded with the goal of detecting germinal cell mutagens, which remains unfulfilled.
- Genetic toxicology research has primarily focused on detecting carcinogens using non-mammalian or in vitro assays, often examining somatic cell mutations.
- This approach has led to a 25-year quest for a definitive short-term assay and an overemphasis on somatic cell effects.
Purpose of the Study:
- To critically re-evaluate the strategies employed in genetic toxicology over the past 25 years.
- To highlight the need to shift focus towards detecting germinal cell mutagens.
- To advocate for the development of robust animal and human germinal cell assays and expand biomonitoring for chronic low-level exposures.
Main Methods:
- Review of historical approaches in genetic toxicology and carcinogen detection.
- Analysis of the limitations of non-mammalian and in vitro assays for germinal mutagenicity.
- Proposal for future research directions including animal and human germinal cell assays and genetic biomonitoring.
Main Results:
- The field has largely focused on somatic cell mutations, neglecting the crucial area of germinal cell mutagenicity.
- Non-mammalian and in vitro assays have proven insufficient for comprehensive carcinogen characterization, particularly for germinal effects.
- A significant gap exists in evaluating the impact of chronic low-level exposure to potential carcinogens on human populations.
Conclusions:
- The field of genetic toxicology needs to re-establish credibility by addressing the unfulfilled goal of detecting germinal cell mutagens.
- Future research should prioritize the development of suitable germinal cell assays in animals and humans.
- Expanding genetic biomonitoring is essential for evaluating chronic low-level exposures and their impact on human health.
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