Related Experiment Video
Updated: May 9, 2026
![Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F60445.jpg&w=3840&q=50)
Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
Published on: December 19, 2019
Early changes in proteome levels upon acute deltamethrin exposure in mammalian skin system associated with its
Jasmine George1, Yogeshwer Shukla
1Proteomics Laboratory, Indian Institute of Toxicology Research, Council of Scientific & Industrial Research (CSIR), India.
Abstract:
Deltamethrin, a pyrethroid insecticide, used extensively for pest control has been reported to cause adverse health effects including carcinogenic/toxic effects in animals but the underlying mechanism remains elusive. In the present study, we investigated the effect of deltamethrin after short exposure on early protein expression changes involved in neoplastic transformation in mouse skin, validated the results in human keratinocyte HaCaT cells and thereby explore the possible underlying mechanism. Deltamethrin (4 mg/kg b.wt) and benzo[a]pyrene (B[a]P, 0.05 mg/kg b.wt) were topically applied on Swiss albino mice, respectively. The comparative protein expression profiles with vehicle control were generated by 2-dimensional gel electrophoresis (2-DE) and mass spectrometry. 2-DE maps of deltamethrin and B[a]P treated mouse skin showed 20 and 24 significant (2 fold change, p < 0.05) differentially expressed protein spots, against vehicle controls. However, comparison between them showed relatively similar expression level of 20 spots. Among them, 5 proteins (carbonic anhydrase III, peroxiredoxin-2, calcyclin, superoxide dismutase [Cu-Zn], ubiquitin) are of particular significance as these are involved in cancer-related key processes. Deregulation of these was confirmed at protein and mRNA levels by immunoblotting and RT-PCR in mouse skin and HaCaT cells. Therefore, we conclude that these preliminarily identified proteins might be responsible for the neoplastic transformation of mouse skin epidermal cells and HaCaT cells by deltamethrin. This study proposes complementary mechanism where inhibition of proteasome activator protein (PA200) is responsible for accumulation of ubiquitinated-calcyclin, regulates deltamethrin-induced neoplastic changes in mouse skin and HaCaT cells.
Insights
Deltamethrin exposure alters key cancer-related protein expression in mouse skin and human cells, suggesting a mechanism for its neoplastic effects. This study identifies specific proteins involved in deltamethrin-induced skin cell changes.
Area of Science:
- Toxicology
- Molecular Biology
- Cancer Research
Background:
- Deltamethrin, a pyrethroid insecticide, is widely used but its carcinogenic mechanisms are unclear.
- Previous studies suggest potential adverse health effects, including carcinogenicity, in animals.
Purpose of the Study:
- To investigate deltamethrin's effects on early protein expression changes linked to neoplastic transformation.
- To explore the underlying molecular mechanisms in mouse skin and human keratinocyte (HaCaT) cells.
Main Methods:
- Topical application of deltamethrin and benzo[a]pyrene on mouse skin.
- Comparative proteomic analysis using 2-dimensional gel electrophoresis and mass spectrometry.
- Validation of protein and mRNA deregulation via immunoblotting and RT-PCR.
Main Results:
- Deltamethrin and benzo[a]pyrene induced significant differential protein expression in mouse skin.
- Five key proteins (carbonic anhydrase III, peroxiredoxin-2, calcyclin, superoxide dismutase [Cu-Zn], ubiquitin) involved in cancer-related processes were identified.
- Deregulation of these proteins was confirmed at both protein and mRNA levels in mouse skin and HaCaT cells.
Conclusions:
- The identified proteins may contribute to deltamethrin-induced neoplastic transformation in skin cells.
- A proposed mechanism involves the inhibition of proteasome activator protein (PA200), leading to ubiquitinated-calcyclin accumulation and neoplastic changes.
