Secondhand smoke promotes chemical toxicity in fetal lung
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Secondhand tobacco smoke is associated with increased asthma, pneumonia, bronchitis, heart disease and cancer. Mothers who smoke deliver children who have low birth weights and have reduced lung function. These children have more lung diseases such as asthma and bronchiolitis. These conditions are likely the result of abnormalities in lung growth and abnormalities of certain specialized protective mechanisms that are present in the lung. From laboratory studies, secondhand smoke is known to cause changes in the types of cells which line the smallest airways in the lung. These cells have unique capabilities which help maintain healthy lungs by eliminating or inactivating pollutants which we inhale. Functioning much like cells in the liver, these cells transform toxic pollutants into harmless compounds which can be removed through the blood stream. 
 
 
 
 
 
 This specialized cellular system is known as the cytochrome P450 monooxygenase system and consists of a family of enzymes, each with unique specificities to certain common, but harmful, environmental pollutants. Secondhand smoke is known to injure this system and there is concerning evidence that injury to the P450 monooxygenase system may be responsible for some of the disease which is associated with prolonged exposure to secondhand smoke. 
 
 
 
 
 
 This proposal will examine the effect of maternal smoke exposure on a member of the cytochrome P450 monooxygenase family known as CYP1A1. CYP1A1 is activated by cigarette smoke. Unlike certain other P450 mono-oxygenases, CYP1A1 can activate, rather than inactivate, certain environmental pollutants into toxic compounds. High levels of CYP1A1 are associated with the development of lung cancer. Also, there is evidence that high levels of CYP1A1 may worsen lung damage when the lung is exposed to high levels of oxygen, such as in a person requiring intensive respiratory support with a mechanical ventilator. This finding also raises the possibility that CYP1A1 may be important in the lungs response to ozone, the major pollutant in smog. 
 
 
 
 
 
 In this proposal, a well characterized model in laboratory rats that mimics secondhand smoke exposure in the human lung, is used to examine whether fetal exposure to secondhand smoke changes the normal level gene expression and enzyme activity of CYP1A1. This proposal addresses an important and specific mechanism in which pregnant mothers exposed to secondhand smoke give birth to children whose lungs have adverse changes in P450 mono-oxygenase metabolism that render them more susceptible to pollutants. This model will specifically address whether fetal exposure to secondhand smoke imprints sustained and dangerous levels of CYP1A1 production after birth. The information learned in these investigat-ions will help scientists and physicians under-stand how secondhand smoke and other pollutant exposures lead to worsening of asthma, bronchitis and other respiratory diseases.