天美传媒

Personalized Toxicology; Pharmacogenomics; Genetic Susceptibility; Biomarkers; Toxicology; Environmental Exposures; Adverse Drug Reactions; Risk Assessment; Precision Medicine

Introduction

Toxicology is the study of the adverse effects of chemicals, drugs, and environmental factors on living organisms. Traditionally [1], toxicology relied on generalized models that assumed a one-size-fits-all approach to understanding how toxicants affect human health. However, this approach often failed to account for individual variability in response to exposure. Personalized toxicology seeks to address this limitation by tailoring risk assessments, prevention strategies, and therapeutic interventions based on an individual’s genetic makeup, lifestyle, and environmental exposures [2].

The core concept of personalized toxicology revolves around recognizing that people are not all alike in how they metabolize, process, or react to toxic substances. Genetic factors, such as polymorphisms in enzymes involved in drug metabolism, can significantly influence how a person responds to a drug or environmental toxin. Personalized toxicology combines insights from genomics, proteomics, metabolomics, and environmental science to develop strategies that are customized to an individual’s unique characteristics [3].

Mechanisms of Personalized Toxicology

Genetic variability in toxicology: One of the key pillars of personalized toxicology is understanding how genetic factors influence toxicity. Genetic polymorphisms in drug-metabolizing enzymes, transporters, and receptors can have a significant impact on an individual’s response to toxins and drugs. For example, enzymes in the cytochrome P450 family, which are responsible for metabolizing a wide variety of substances, can vary in their activity based on genetic variation. Some individuals have polymorphisms that lead to poor metabolism of certain drugs, while others may have hyperactive enzymes that accelerate drug metabolism, potentially reducing efficacy or causing harmful metabolites [4].

Other genetic variations can affect an individual’s ability to repair DNA damage caused by environmental toxicants or drugs. For example, polymorphisms in the genes responsible for the repair of oxidative DNA damage (such as GSTs or XRCC1) can increase the susceptibility to cancers caused by chemical exposures or radiation [5].

Biomarkers and monitoring: Personalized toxicology relies heavily on biomarkers to identify early signs of toxicity and assess an individual’s risk. Biomarkers can be measured in various biological samples, such as blood, urine, or saliva, to provide real-time data on exposure to toxicants and the subsequent biological responses. For example, elevated levels of liver enzymes, such as alanine aminotransferase (ALT), can indicate liver damage caused by drug-induced hepatotoxicity.

Moreover, the use of genetic biomarkers allows for more precise prediction of toxicity. For instance, genetic testing for mutations in the TPMT gene can predict whether a patient is at risk of thiopurine-induced toxicity, commonly seen in individuals with leukemia or autoimmune diseases undergoing treatment with drugs like azathioprine [6].

Environmental exposures and lifestyle factors: The integration of environmental exposure data is another important aspect of personalized toxicology. The way an individual is exposed to environmental toxins, such as air pollutants, heavy metals, or pesticides, can vary significantly depending on geographical location, occupation, and lifestyle. Personal exposure monitoring, through wearable devices or environmental sensors, can provide data that complement genetic information to create a more complete picture of an individual’s risk profile [7].

For example, individuals working in occupations that expose them to hazardous chemicals, such as factory workers or agricultural laborers, may be at greater risk of developing cancer or neurological disorders due to their heightened exposure. Personalized toxicology helps tailor interventions based on specific occupational risks and exposure levels.

Applications of Personalized Toxicology

Adverse drug reactions (ADRs): One of the most important applications of personalized toxicology is the prevention and management of adverse drug reactions (ADRs). ADRs are a significant cause of morbidity and mortality, with genetic factors playing a key role in their occurrence. By identifying genetic predispositions to ADRs, clinicians can select drugs and dosages that are better suited to an individual’s genetic makeup, improving therapeutic outcomes and minimizing harm.

For instance, certain genetic variants in the CYP2C9 and VKORC1 genes can influence an individual’s response to warfarin, an anticoagulant drug. Genetic testing prior to treatment can help determine the appropriate dosage, reducing the risk of bleeding complications or treatment failure.

Additionally, pharmacogenomic testing for polymorphisms in the HLA-B gene can help predict severe allergic reactions, such as Stevens-Johnson syndrome, caused by drugs like carbamazepine and allopurinol.

Cancer risk and chemotherapy: Personalized toxicology is also used in cancer therapy to predict the risk of toxicity from chemotherapy. Chemotherapeutic agents, such as cyclophosphamide and methotrexate, can cause significant side effects, including organ toxicity and bone marrow suppression. Genetic testing can help identify individuals who may be more susceptible to these toxicities and allow for personalized dosing regimens or alternative treatments.

For example, individuals with mutations in the TPMT gene are at risk for severe bone marrow toxicity from thiopurine drugs, commonly used in the treatment of leukemia and inflammatory bowel disease. Genetic testing can help identify these individuals before treatment, guiding clinicians to adjust the drug dosage or choose a different therapy to minimize the risk of harm.

Environmental toxicology and public health: Personalized toxicology also has significant applications in public health, particularly in the assessment of environmental exposures and their impacts on health. By integrating genetic data with environmental exposure information, it is possible to identify individuals at higher risk of developing diseases due to exposure to air pollutants, industrial chemicals, or other environmental toxicants.

For example, certain genetic polymorphisms in antioxidant defense genes can make individuals more susceptible to lung diseases caused by exposure to environmental toxins, such as tobacco smoke or air pollution. Personalized risk assessments can help target interventions to protect vulnerable populations, such as children or the elderly, from environmental hazards.

Future Directions of Personalized Toxicology

Advancements in Genomic Technologies

As genomic technologies continue to improve, the ability to perform high-throughput genetic testing and analyze large datasets will enable more accurate predictions of individual susceptibility to toxicants. Advances in whole-genome sequencing, RNA sequencing, and CRISPR technology could provide deeper insights into how genetic variants contribute to toxicological responses.

Moreover, the development of personalized toxicology models based on in vitro systems, such as organ-on-a-chip technology or induced pluripotent stem cells (iPSCs), could help simulate the effects of toxins on human tissues, allowing for more precise risk assessments and drug testing.

Integration of Multi-Omics Data

The future of personalized toxicology will also involve the integration of multi-omics data, combining genomics, transcriptomics, proteomics, and metabolomics. This holistic approach will provide a more comprehensive understanding of how toxicants affect individuals at the molecular level and allow for the identification of new biomarkers of toxicity. By integrating these data with environmental exposure profiles, researchers can develop predictive models that improve risk assessment and enhance personalized treatment strategies.

Regulatory and Ethical Considerations

As personalized toxicology becomes more widely implemented, there will be increasing challenges related to regulatory standards, data privacy, and ethical considerations. Ensuring that genetic testing and environmental exposure data are used ethically and responsibly will be crucial. Additionally, regulatory bodies will need to establish guidelines for integrating personalized toxicology into clinical practice and public health interventions.

Conclusion

Personalized toxicology is poised to revolutionize the field of toxicology by offering individualized risk assessments, improving drug safety, and optimizing treatment regimens. By combining genetic information, biomonitoring, and environmental exposure data, personalized toxicology can enhance our understanding of how toxins affect human health and lead to more precise interventions. While there are still challenges to overcome, including the integration of multi-omics data and the ethical implications of genetic testing, the potential benefits of personalized toxicology for improving public health are immense.

1. Ji H, Huang W, Xing Z, Zuo J, Wang Z, et al. (2019) . Sci Rep 9: 8271.

, ,

2. Le Borgne S, Paniagua D, Vazquez-Duhalt R (2008) . J Mol Microbiol Biotechnol 15: 74-92.

, ,

3. Jurate V, Mika S, Petri L (2002) . Sci Total Environ 289: 97-121.

, ,

4. Zhiping S, Hui Z, Yunhong Z (2010) . Angew Chem Int Ed 49: 8444-8448.

, ,

5. Cavallaro G, Lazzara G, Milioto S (2010) J Surf Colloids 27: 1158-1167.

, ,

6. Lee J, Cameron I, Hassall M (2019) Process Saf Environ Prot 132: 325-339.

, ,

7. Baraud F, Tellier S, Astruc M (1997) . J. Hazard Mater 56: 315-332.

,