Toxicology and safety testing are central to biomedical science, pharmaceutical development, and regulatory approval. Before drugs, chemicals, or medical devices reach clinical trials or consumer use, they must be evaluated for safety and potential harm. While animal studies have historically played a dominant role, immortalised cell lines now provide a reproducible, ethical, and scalable alternative for testing.
Cell lines derived from tumours, primary tissues, or transformed cells allow researchers to explore toxicity mechanisms in organ-specific contexts. They offer insight into how compounds interact with human biology, highlighting risks and guiding safer therapeutic design. The following sections explore ten widely used cell lines and their role in toxicology.
HeLa Cells and Cytotoxicity Assays
The versatility of HeLa cells extends far beyond cancer biology into toxicological testing. Their rapid proliferation and resilience under laboratory conditions make them ideal for early cytotoxicity assays, where compounds are screened for their ability to kill or inhibit cell growth.
HeLa cells have been used to:
- Evaluate dose-dependent effects of chemotherapeutics.
- Screen natural products for anticancer potential.
- Investigate genotoxicity through chromosomal damage assays.
Despite their advantages, their highly mutated genome can complicate interpretation, as they may respond differently from normal human cells. Nevertheless, HeLa cells remain a first-line tool for high-throughput toxicology because of their robustness and sensitivity to cytotoxic compounds.
HEK293 as a Model for Receptor Toxicity
HEK293 cells are indispensable in pharmacological toxicology. Their ability to be transfected with human receptors or ion channels allows scientists to test how compounds affect signalling systems.
They play a critical role in:
- Cardiotoxicity testing, particularly for drugs interacting with cardiac ion channels.
- Neurotoxicity assays, through expression of neurotransmitter receptors.
- Gene editing safety, where CRISPR and viral vectors are assessed for off-target effects.
HEK293 cells act as a flexible test system for compound–receptor interactions, predicting adverse drug reactions that could otherwise emerge in clinical use.
CHO Cells and Biocompatibility of Therapeutics
In the realm of industrial biotechnology, CHO cells are not only the primary hosts for therapeutic protein production but also crucial for safety testing of biopharmaceuticals. Because they generate human-like post-translational modifications, CHO systems allow for early toxicity profiling of recombinant proteins.
Applications include:
- Assessing immunogenicity risk in monoclonal antibodies.
- Screening for protein misfolding or aggregation that may trigger adverse effects.
- Evaluating stability and tolerance of formulations before animal studies.
CHO cells ensure biologics are both effective and safe, underscoring their role as both producers and testers in modern biopharmaceutical pipelines.
SH-SY5Y and Neurotoxicology
Neurotoxicity is a major safety concern in drug development, and SH-SY5Y cells are among the most frequently used neuronal models. These neuroblastoma-derived cells can differentiate into neuron-like phenotypes, making them suitable for evaluating compound effects on neuronal survival and signalling.
They are widely used to test:
- Environmental toxins, such as pesticides and heavy metals.
- Experimental drugs for unintended effects on synaptic transmission.
- Mechanisms of oxidative stress and mitochondrial dysfunction.
By reproducing key aspects of neuronal physiology, SH-SY5Y provides a reproducible, cost-effective tool for neurotoxicology and safety pharmacology.
MCF7 in Hormone-Related Toxicology
The MCF7 breast cancer line offers a unique window into endocrine toxicology. Because these cells express oestrogen receptors, they can be used to investigate endocrine-disrupting chemicals and drugs.
MCF7 applications include:
- Detecting oestrogenic activity of environmental pollutants.
- Assessing chemotherapeutic selectivity for hormone-positive tumours.
- Studying apoptotic responses to endocrine-targeting drugs.
The line provides a biologically relevant system to explore how endocrine-active substances may influence hormone-dependent tissues, supporting both toxicological assessment and therapeutic evaluation.
THP1 and Immunotoxicity Testing
Immune-related toxicities can have severe consequences, and THP1 cells provide an essential model for evaluating immune responses. Derived from monocytic leukaemia, THP1 cells can differentiate into macrophage-like cells, allowing for the controlled study of innate immunity.
They are used in:
- Cytokine release assays, essential for predicting immune overstimulation by biologics.
- Pathogen interaction studies, exploring inflammatory responses to toxins and microbes.
- Nanoparticle toxicology, testing how novel drug delivery systems affect immune balance.
Their reproducibility makes them invaluable in regulatory immunotoxicology, where safety evaluation of new therapeutics requires reliable immune system models.
A2780 and Chemotherapy Toxicology
The ovarian carcinoma line A2780 has become indispensable for testing chemotherapeutic drugs. Their sensitivity to platinum-based compounds makes them a key model for evaluating both therapeutic effects and toxic side effects.
Through A2780 studies, researchers can:
- Identify DNA damage thresholds that separate therapeutic benefit from toxicity.
- Explore cross-resistance with other drug classes.
- Assess novel drug derivatives with potentially lower toxicity profiles.
These cells highlight how tumour-specific lines can act as test beds for evaluating not just efficacy but also the toxicological boundaries of chemotherapy.
HL-60 and Haematotoxicity Studies
Haematopoietic toxicity remains a major limitation of many drugs, and HL-60 cells are widely employed in blood toxicity studies. Originating from acute promyelocytic leukaemia, they can be induced into granulocytic or monocytic lineages.
HL-60 lines contribute to:
- Screening anticancer drugs for effects on bone marrow progenitors.
- Testing environmental toxins that impair blood cell formation.
- Evaluating apoptotic pathways in response to cytotoxic compounds.
By simulating the impact of drugs and chemicals on developing blood cells, HL-60 remains crucial for understanding haematological safety risks.
Caco-2 and Intestinal Permeability
Caco-2 cells, derived from colon carcinoma, are a cornerstone in gastrointestinal toxicology. When cultured, they differentiate into enterocyte-like cells that replicate intestinal absorption properties.
They are particularly useful for:
- Permeability assays, determining whether drugs cross the intestinal barrier.
- Barrier function testing, predicting gastrointestinal irritation or disruption.
- Nutrient and xenobiotic interactions, modelling dietary and chemical exposure effects.
Caco-2 permeability testing has become a regulatory standard for oral drug candidates, underscoring its role in safety evaluation.
HepG2 and Hepatotoxicity Screening
HepG2 cells, derived from hepatocellular carcinoma, are central to hepatotoxicity studies. Because the liver is the primary organ for drug metabolism, hepatotoxicity remains a leading cause of clinical trial failures and post-market withdrawals.
HepG2 assays are used to:
- Detect dose-dependent liver toxicity in new compounds.
- Examine metabolism of xenobiotics and drug–drug interactions.
- Study lipid accumulation and steatosis in metabolic disease contexts.
Although not as metabolically complete as primary hepatocytes, HepG2 cells offer scalability and reproducibility for high-throughput toxicology.
Conclusion
Immortalised cell lines have become indispensable in toxicology and safety testing. HeLa provides rapid cytotoxicity screening, HEK293 models receptor-mediated toxicity, and CHO ensures biopharmaceutical safety. SH-SY5Y supports neurotoxicology, MCF7 enables endocrine disruption studies, and THP1 assists in immunotoxicity evaluation. A2780 offers chemotherapy-specific insights, HL-60 models blood toxicity, Caco-2 predicts intestinal absorption, and HepG2 remains essential for hepatotoxicity.
Together, these cell lines reduce reliance on animal testing, improve predictive accuracy for human safety, and accelerate the development of safer drugs and chemicals. By capturing the physiological and pathological dimensions of toxicity, they serve as essential tools for bridging laboratory discoveries with public health protection.
