Abstract
Birth is characterized by an intense oxidative stress resulting in nucleotide alterations and gene overexpression in mouse lung. We showed that cigarette smoke (CS) is carcinogenic when exposure starts soon after birth and applied this bioassay to evaluate the efficacy of chemopreventive agents. The present study evaluated whether administration of the antioxidants N-acetyl-L-cysteine (NAC) and vitamin C or ascorbic acid (AsA) during pregnancy can protect strain H Swiss mice exposed to CS after birth. Exposure to CS, for 4 months, of newborns from untreated mice resulted in significant alterations at 8 months of life, including alveolar epithelial hyperplasia, emphysema, blood vessel proliferation, microadenomas, adenomas, and malignant tumors in lung, liver parenchymal degeneration and urinary bladder epithelium hyperplasia. Treatment throughout pregnancy with either NAC, a scavenger of reactive oxygen species, or AsA, an electron donor, did not affect fertility, parity, and body weight of newborns. Prenatal antioxidants significantly inhibited most lesions in adult mice exposed to CS since birth. For instance, the incidence of emphysema was reduced from 27.5% in CS-exposed mice that were untreated during pregnancy to 7.1% and 14.0% in those treated prenatally with NAC and AsA, respectively. Lung adenomas were reduced from 34.8% to 16.7% and 9.3%, respectively. Malignant lung tumors were reduced from 13.0% to 4.7% by prenatal AsA. Liver parenchymal degeneration was reduced from 58.0% to 14.3% by prenatal NAC. These data mechanistically support a “transplacental chemoprevention” strategy, aimed at protecting the newborn from oxidative stress and the adult from CS-related diseases appearing later in life.
Keywords: Antioxidants, ascorbic acid, cigarette smoke, emphysema, Lung cancer, N-acetyl-L-cysteine, pregnancy, reduced glutathione, Barker hypothesis
Current Cancer Drug Targets
Title: Transplacental Antioxidants Inhibit Lung Tumors in Mice Exposed to Cigarette Smoke After Birth: A Novel Preventative Strategy?
Volume: 12 Issue: 2
Author(s): R. Balansky, G. Ganchev, M. Iltcheva, V. E. Steele and S. De Flora
Affiliation:
Keywords: Antioxidants, ascorbic acid, cigarette smoke, emphysema, Lung cancer, N-acetyl-L-cysteine, pregnancy, reduced glutathione, Barker hypothesis
Abstract: Birth is characterized by an intense oxidative stress resulting in nucleotide alterations and gene overexpression in mouse lung. We showed that cigarette smoke (CS) is carcinogenic when exposure starts soon after birth and applied this bioassay to evaluate the efficacy of chemopreventive agents. The present study evaluated whether administration of the antioxidants N-acetyl-L-cysteine (NAC) and vitamin C or ascorbic acid (AsA) during pregnancy can protect strain H Swiss mice exposed to CS after birth. Exposure to CS, for 4 months, of newborns from untreated mice resulted in significant alterations at 8 months of life, including alveolar epithelial hyperplasia, emphysema, blood vessel proliferation, microadenomas, adenomas, and malignant tumors in lung, liver parenchymal degeneration and urinary bladder epithelium hyperplasia. Treatment throughout pregnancy with either NAC, a scavenger of reactive oxygen species, or AsA, an electron donor, did not affect fertility, parity, and body weight of newborns. Prenatal antioxidants significantly inhibited most lesions in adult mice exposed to CS since birth. For instance, the incidence of emphysema was reduced from 27.5% in CS-exposed mice that were untreated during pregnancy to 7.1% and 14.0% in those treated prenatally with NAC and AsA, respectively. Lung adenomas were reduced from 34.8% to 16.7% and 9.3%, respectively. Malignant lung tumors were reduced from 13.0% to 4.7% by prenatal AsA. Liver parenchymal degeneration was reduced from 58.0% to 14.3% by prenatal NAC. These data mechanistically support a “transplacental chemoprevention” strategy, aimed at protecting the newborn from oxidative stress and the adult from CS-related diseases appearing later in life.
Export Options
About this article
Cite this article as:
Balansky R., Ganchev G., Iltcheva M., E. Steele V. and De Flora S., Transplacental Antioxidants Inhibit Lung Tumors in Mice Exposed to Cigarette Smoke After Birth: A Novel Preventative Strategy?, Current Cancer Drug Targets 2012; 12 (2) . https://dx.doi.org/10.2174/156800912799095153
DOI https://dx.doi.org/10.2174/156800912799095153 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Dysregulated Chemokine Signaling in Cystic Fibrosis Lung Disease: A Potential Therapeutic Target
Current Drug Targets Liposomal Irinotecan in the Treatment of Refractory Pancreatic Cancer
Recent Patents on Anti-Cancer Drug Discovery Identification of Two Novel Mutations in the <i>ATM</i> Gene from Patients with Ataxia-Telangiectasia by Whole Exome Sequencing
Current Genomics A Novel Method to Synthesize 4-Aryl-1H-1,2,3-Triazoles and its Antihepatoma Activity
Anti-Cancer Agents in Medicinal Chemistry Reprogrammed Metabolism of Cancer Cells as a Potential Therapeutic Target
Current Pharmaceutical Design Hemolytic Uremic Syndrome in Children
Current Pediatric Reviews Direct Modification of Bioactive Phenothiazines by Exposure to Laser Radiation
Recent Patents on Anti-Infective Drug Discovery Genetic Susceptibility to Endometrial Cancer
Current Women`s Health Reviews Cancer Pharmacogenomics: Germline DNA, Tumor DNA, or Both?
Current Pharmacogenomics Combining Quantum-Behaved PSO and K2 Algorithm for Enhancing Gene Network Construction
Current Bioinformatics Current Constructs and Targets in Clinical Development for Antibody- Based Cancer Therapy
Current Drug Targets Antiangiogenic Therapy
Current Pharmaceutical Design Clinical Pharmacokinetics of Systemically Administered Antimycotics
Current Clinical Pharmacology Equilibrative Nucleoside (ENTs) and Cationic Amino Acid (CATs) Transporters: Implications in Foetal Endothelial Dysfunction in Human Pregnancy Diseases
Current Vascular Pharmacology Functional Neuroimaging of Stimulation by Music Using Positron Emission Tomography
Current Medical Imaging Impact of Renin-Angiotensin System in Hepatocellular Carcinoma
Current Cancer Drug Targets Functions of S100 Proteins
Current Molecular Medicine uPAR as Anti-Cancer Target: Evaluation of Biomarker Potential, Histological Localization, and Antibody-Based Therapy
Current Drug Targets Strategies to Optimize the Effectiveness of Antifungal Treatment for Invasive Aspergillosis
Anti-Infective Agents Current and Potential Anticancer Drugs Targeting Members of the UHRF1 Complex Including Epigenetic Modifiers
Recent Patents on Anti-Cancer Drug Discovery