About this Research Topic
Because testing the effect of toxicants directly in humans is unethical, addressing chemical toxicity in humans and, especially, the variability of human responses to chemicals is the principal problem for population-wide toxicological testing. The variability of human responses to chemical exposures, including drugs and environmental toxicants, cannot be correctly assessed in animal models. However, human variability in response to toxicants can be accessed at the cellular level by using donor-specific cells.
Cellular functional responses can potentially portray individual sensitivity to environmental toxicants. This approach utilizes the classical gene-environment paradigm with the advantage of encompassing the integrated genetic background and the dynamics of cellular metabolism. Furthermore, this approach provides an opportunity for examining the role of specific cellular organelles, including mitochondria, in the variability of donor-specific responses. Assessing individual differences in functional responses can potentially generate interpretable data with actionable information, whereas the functional significance of a genetic marker is often unknown.
Testing functional cellular responses to a specific factor is similar to the challenge testing, such as classical oral glucose tolerance test use to determine susceptibility to type 2 diabetes. Another example is stress test, an exercise test used for the diagnosis of cardiovascular disease. The main purpose of such testing is to rank the individuals as more or less susceptible to a challenge. Cell-based testing using an environmental challenge follows the same concept and can be used as a basis for risk stratification in epidemiological studies.
This Research Topic aims to provide an interdisciplinary perspective on the potential of moving epidemiology to a new level in the characterization of individual susceptibility to environmental exposures. We invite contributions from cellular biologists, toxicologists, and epidemiologists to discuss the principals of using cells as a proxy of individual responses as well as the current use of personalized cell-based assays, including topics such as:
1) Which donor-specific cells could be used as a proxy for an individual in characterizing cellular response to a specific exposure?
2) How can we validate the biological plausibility of such cellular models based on what is known about the mechanistic effects of the toxicants?
3) What methodologies can be used to study inter- and intra-individual variability of cellular responses?
4) How should donor-specific data on functional cellular responses be integrated with computational toxicological models?
5) How should the connection between cell-based testing and an epidemiological outcome in prospective studies be analyzed?
Keywords: Epidemiology, Susceptibility, Low-dose exposure cell-based assays, individual variability, risk stratification
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