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Title: De parentale effecten van roken op de genetische integriteit van het nageslacht.
Authors: VAN HAASTERT, Rick
Advisors: GODSCHALK, R.
Issue Date: 2007
Publisher: tUL
Abstract: Smoking is a major cause of death, because of an increased risk of cardiovascular decease and cancer. Smoking doesn’t only affect the smoker him or herself, but also their unborn children. Cigarette smoke contains polycyclic aromatic hydrocarbons (PAHs), of which benzo[a]pyrene (B[a]P) is the most researched. The body will metabolize xenobiotics in an effort to excrete them. Phase 1 metabolic enzymes, such as the cytochrome p450 family, depend on oxidation to make xenobiotics more excretable. Phase 2 enzyms such as glutathione-S-transferases and N-acetyltransferases detoxify xenobiotics with redox reactions. B[a]P is metabolized by members of the cytochrome p450 enzyme family to B[a]P diol-epoxide (BPDE), which is highly cytotoxic, carcinogenic and mutagenic. BPDE binds covalent to DNA, forming DNA adducts which can cause mutations and chromosome aberrations. The rate at which the body activates or detoxifies xenobiotics differs between individuals, due to small differences in the genetic code for the metabolic enzymes, called polymorphisms. Male smoking has a negative effect on the sperm quality. To investigate if spermatogonial cells are capable of metabolizing B[a]P, if they are sensitive to exposure to B[a]P and BPDE and if they form DNA adducts after exposure and are able to repair them, a cytotoxic and clonogenic assay and 32P-postlabeling was performed on mouse spermatogoniale CG-1 spg cells. CG-1 spg cells have a sharp decrease in viability and reproducibility after exposure to more then 1 μM BPDE. CG-1 spg cells are capable of metabolizing B[a]P, resulting in an increase in DNA adducts. CG-1 spg cells are not fully capable in repairing these DNA adducts. Pregnant women who smoke have a higher risk of premature births and prenatal deaths. To investigate the effects of female smoking on there offspring and the role of polymorphisms in metabolic genes, 65 smoking and non smoking mother-child pairs were selected and genotyping was preformed. Smoking mothers and their children have a significantly higher level of DNA adducts compared to non smoking mothers and their children. A higher level of risk polymorphisms is related to a higher level of DNA adducts in smoking mothers and child. The effects of single polymorphisms couldn’t be investigated due to the small number of subjects. Male and female smoking adversely affects the child, either by a decrease in sperm quality or by affecting the pregnancy. Spermatogonial cells are sensitive to the damaging effects of cigarette smoke constituents such as B[a]P and its metabolite BPDE. A higher level of risk polymorphisms in the genetic code of metabolic genes are related to a higher level DNA adducts in smokers. The role of DNA repair mechanisms needs to be further investigated.
Notes: Master in de biomedische wetenschappen - klinische en moleculaire wetenschappen
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Category: T2
Type: Theses and Dissertations
Appears in Collections:Master theses

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