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Updated: Mar 30, 2026
Using Nicotine in a Silica-Exposed Mouse Model to Promote Lung Epithelial-Mesenchymal Transition
Published on: March 3, 2023
C. elegans and mutants with chronic nicotine exposure as a novel model of cancer phenotype
Rajani Kanteti1, Immanuel Dhanasingh1, Essam El-Hashani2
1a Department of Medicine , Section of Hematology/Oncology, University of Chicago , Chicago , IL , USA.
Abstract:
We previously investigated MET and its oncogenic mutants relevant to lung cancer in C. elegans. The inactive orthlogues of the receptor tyrosine kinase Eph and MET, namely vab-1 and RB2088 respectively, the temperature sensitive constitutively active form of KRAS, SD551 (let-60; GA89) and the inactive c-CBL equivalent mutants in sli-1 (PS2728, PS1258, and MT13032) when subjected to chronic exposure of nicotine resulted in a significant loss in egg-laying capacity and fertility. While the vab-1 mutant revealed increased circular motion in response to nicotine, the other mutant strains failed to show any effect. Overall locomotion speed increased with increasing nicotine concentration in all tested mutant strains except in the vab-1 mutants. Moreover, chronic nicotine exposure, in general, upregulated kinases and phosphatases. Taken together, these studies provide evidence in support of C. elegans as initial in vivo model to study nicotine and its effects on oncogenic mutations identified in humans.
Insights
This study shows that chronic nicotine exposure in C. elegans impacts fertility and locomotion in mutants with oncogenic mutations relevant to lung cancer. Nicotine affects egg-laying and movement, highlighting C. elegans as a model for studying nicotine
Area of Science:
- * Molecular biology
- * Genetics
- * Toxicology
Background:
- * MET and its oncogenic mutants are implicated in lung cancer.
- * C. elegans serves as a model organism for genetic and toxicological studies.
- * Nicotine's effects on cellular pathways and cancer mutations require investigation.
Purpose of the Study:
- * To investigate the effects of chronic nicotine exposure on C. elegans mutants with oncogenic mutations relevant to lung cancer.
- * To assess the impact of nicotine on fertility, egg-laying capacity, and locomotion in these mutants.
- * To evaluate the utility of C. elegans as an in vivo model for studying nicotine's effects on human oncogenic mutations.
Main Methods:
- * Utilized C. elegans strains with mutations in vab-1 (Eph ortholog), RB2088 (MET ortholog), SD551 (KRAS mutant), and sli-1 (c-CBL equivalent).
- * Subjected mutant strains to chronic nicotine exposure.
- * Assessed egg-laying capacity, fertility, and locomotion (circular motion and overall speed).
- * Analyzed changes in kinase and phosphatase activity.
Main Results:
- * Chronic nicotine exposure significantly reduced egg-laying capacity and fertility in most tested mutants.
- * The vab-1 mutant showed increased circular motion, while other mutants did not exhibit this specific response.
- * Locomotion speed increased with nicotine concentration in all mutants except vab-1.
- * Nicotine exposure generally upregulated kinases and phosphatases.
Conclusions:
- * C. elegans is a viable in vivo model for studying the effects of nicotine on oncogenic mutations.
- * Nicotine exposure negatively impacts reproductive functions and alters locomotion in specific genetic backgrounds.
- * The study provides insights into the molecular mechanisms underlying nicotine's effects on cancer-related pathways.
