Seminar Extra Credit Summary (for Lab)

Steven R. Meyers, Ph.D Assistant Professor,

Dept. of Pharmacology and Toxicology,

University of Louisville School of Medicine

Tobacco Smoking During Pregnancy – Biomarkers of Exposure & the

Relationship to Genetics

In the state of Kentucky, 30% of mothers smoke. This causes the baby to get less food and oxygen.  As a result, there are higher rates of miscarriage, still births, premature births, low birth weights, placenta previa, low IQ levels, ADHD, and infants dying of SIDS (Sudden Infant Death Syndrome).  If the child is exposed to second hand smoke during the first two years of life they may get ear infections, asthma or bronchitis, and pneumonia.

We know that tobacco smoke causes cancer, respiratory disease, cardiovascular disease, and cerebrovascular disease in adults. Children who are exposed to tobacco smoke have a 60% increase of having a lower respiratory disease.  There is also an increase risk of developing asthma, inner ear and other ear infections causing long-term hearing problems, and an increase risk of dying of SIDS.  There is no safe time for a mother to be exposed to tobacco smoke. Although there are no adverse effects during the first two weeks, it causes a difficulty attaching to the ovum.  During the third and eighth weeks embryonic development of organs and tissues can be damaged. The most common effect is cleft lip and cleft palate due to exposure to chemicals like the ones in tobacco smoke.  During the last stages of pregnancy functional defects and problems during birth can occur.

Biomarkers are needed because there are approximately 4000 chemicals in tobacco smoke. This is the leading cause of avoidable cancer death. Biomarkers are molecular, biochemical, or cellular alterations that are measurable in biological media such as human tissue, cells, or fluids.  The earlier the biomarker is detected, the more likely the disease will be stopped.  They can be found in metabolites in the body, DNA adducts, and gene mutations.  Biomarkers are selected by determining if it is related to the disease, if it appeared at a defined stage of disease, if it can be obtain non-invasively, if it can be modulated by eliminating exposure, if it provides specificity, sensitivity, and practicality, and if it is stable and easy to measure.

Amniotic fluid can be a biomarker during the first trimester because it protects the fetus. It is filled with urine from the fetus and can tell what the fetus has been exposed to.  During a study where women had an amniocentesis, 1-Hydroxypyrene and Benzo(a)pyrenes were detected and the levels increased as the amount of cigarettes smoked increased.  Hemoglobin can also be a biomarker of carcinogens and tobacco smoke exposure.

Since amino acids undergo nucleophilic substitution with electrophiles in tobacco chemicals, looking at the enzymes that are responsible for getting rid of chemicals in the body is a good place to find biomarkers.  If a person is null genotype they do not have the genes to make these enzymes and are at an increased risk of cancers.  These people often have much more benzo(a)pyrene in the body.  The enzyme N-acetyl transferases activate and deactivate aromatic and heterocyclic amines in the body. If a person does not have this enzyme, they are also at an increased risk.  Fetuses do not develop these enzymes until two years of age.

4-Aminobiphenyl is an aromatic amine that is a strong bladder carcinogen prominent in tobacco smoke.  It is one of the most carcinogenic chemicals in the smoke that we know of.  During a study, it was found that nonsmokers had a very small amount in their system, passively exposed mothers and babies had levels of this chemical, and in smokers the levels increased as the amount of cigarettes smoked increased. 

After all of these studies, it can be seen that there is a correlation of the amount a mother smokes affecting her baby.  It is also observed that the more chemical compounds found in babies, the less they weigh.  The final study showed that there was no difference in African Americans to Caucasians but the amount if Hispanics was much lower in mothers and in the babies.  The birth weights of Hispanic babies were also greater than African Americans and Caucasians.  Overall, this presentation showed that mothers should not smoke during of after pregnancy because the effects are very dangerous and harmful to the baby.