My research group is investigating linkages between the laboratory and field domains to advance an understanding of the generation, fate and health effects of pollutants.  To this point,  we are exploring the generation and fate of oxygenated and polar molecules, for which a paucity of ambient air data exist.  We are also investigating health effects of organochlorines in human populations, for which controversial or little data exist. These areas of research embody two key issues - health effects of endocrine disruptors in human populations, and mechanisms affecting the generation of ozone and fine particulate matter.  A common thread between my present and past research is the creation of new approaches to measure trace levels of environmentally relevant molecules in complex mixtures.
 

A.  Linkages Between Measurements of Oxygenated and Polar Organics in Chamber Studies
and the Ambient Environment.

Photooxidation of biogenic and anthropogenic hydrocarbons yields oxygenated polar organics that include carbonyls, dicarbonyls, hydroxy carbonyls, epoxy carbonyls and oxo acids. In the atmosphere, these molecules can exist in the gas phase where they play a critical role in ozone generation by influencing the creation and depletion of radical oxidizing species. These compounds can also partition to particles, where they affect the hygroscopicity and light scattering properties that affect haze formation. Since certain classes of these molecules are mutagenic, carcinogenic, and cause adverse effects on human cardiovascular and respiratory systems, it is conceivable that these species also contribute to increase in cardiovascular and respiratory illnesses during episodes of high air particulate pollution.

Chemical reaction mechanisms that effect the generation of multifunctional oxygenated polar organics were primarily elucidated from product identification studies conducted in chambers. Ambient air data for many of these compounds do not exist because existing methodologies are not suited to measure such species. Thus, the generation and fate of multifunctional oxygenated products in the ambient environment is not well understood. We are uniquely qualified to fill this significant void because we have established that methodologies developed in our laboratory can provide unambiguous identification of carbonyls, dicarbonyls, hydroxy carbonyls and oxo acids in the ambient environment.  By using our methods,  we identified methyl vinyl ketone, methacrolein, methyl glyoxal, glycolaldehyde and hydroxy acetone in Azusa, CA., and methacrolein, methyl vinyl ketone, glyoxal, methyl glyoxal, 3-hydroxy-2-butanone, and hydroxy acetone in Davis, CA. To our knowledge, this is the second report of glycolaldehyde, and the first measurement of hydroxy acetone and 3-hydroxy-2-butanone in ambient air. We also employed these methods to characterize the molecular composition of fine particulate matter collected from diesel exhaust in the Caldecott tunnel, a traffic tunnel between Walnut Creek and Berkeley, CA.  Of the compounds that we identified in fine particulate matter, glyoxal, methyl glyoxal and crotonaldehyde potentially can cause cardiovascular and respiratory illnesses and cancer.

Current research is improving our methods to validate isoprene photochemical models and to gain insight into photochemical reactions in the ambient atmospheric environment.

B. Exploration of Linkages Between Organochlorines, Oxidative DNA Damage and Breast Cancer.

     In California, breast cancer will account for one in every 3 new invasive cancers diagnosed, and one in six cancer related deaths among women.  Genetic predisposition can explain only 36% of the breast cancers for women between age 20 and 29, and 1% of the breast cancers in women over age 80.  Acquired mutations caused by exposure to xenobiotics may thus be a significant cause of breast cancer.  Recent studies establish that organochlorines cause oxidative DNA damage in breast cancer cell lines and calf thymus DNA. An association between oxidative DNA damage and tumors in breast tissue was also observed.  Existing studies exploring relationships between organochlorines and breast cancer in human populations however are contradictory and controversial.  No study has reported congener-specific analyses of  polychlorinated biphenyl (PCBs), or the measurement of such PCBs in combination with measurements of biomarkers of oxidative DNA damage in breast tissue. Thus, at this time no clear relationship exists between: 1) the amount of organochlorines in blood serum or breast tissue and breast cancer, or 2) oxidative DNA damage and breast cancer.  We are investigating such relationships by measuring biologically active polychlorinated biphenyls (PCBs) and pesticides, and 8-hydroxyguanosine, a biomarker of oxidative DNA damage in normal and tumorous tissue.  We have completed the chemical analyses for samples from a population of white women (n=100) and are conducting statistical analysis of the data to explore linkages between oragnochlorines, oxidative DNA damage and breast cancer.

C.  Exploration of Linkages Between Fetal PCB Exposure, Thyroid Function and Neurodevelopment.

      Neurobehavioral deficits exist in the offspring of animals and in infants of mothers exposed to high-levels of PCBs. The neurotoxicity of levels of PCBs typically found in the environment however is not well understood. One study indicates that children born to mothers who consume more PCB contaminated fish than in other populations had lower IQ scores and exhibited behavioral problems.  Although PCBs can be transferred from the mother to the child during breast-feeding, data indicate that transplacental exposure to the fetal brain is the cause for neurotoxicity, and that interference with thyroid function during pregnancy causes mental retardation, hearing loss and poor muscular coordination.  The structural similarity of PCBs to thyroid hormones enables competitive binding of these organochlorines to proteins (in humans, thyroxine-binding globulin and transthyretin that facilitate the transport of the thyroid hormone, thyroxine (T4) in plasma to the fetus.  A paucity of data however exists on the relationship between levels of specific PCB congeners, thyroid function and long-term development. To address this void, we are investigating linkages between PCBs in the sera of pregnant women who delivered in 1964-1967 and hypothyroid-like intellectual and neurological deficits in the newborn and five-year-old child.  The population for this study is pregnant women in the 1960s receiving prenatal care at one of several Kaiser Health Foundation clinics in the San Francisco Bay Area. The levels of PCBs in the blood are typical of modern day levels. We have completed congener specific analysis for PCBs in 400 blood sera samples, and are collaborating with the principal investigator of the grant, an epidemiologist to explore associations between levels of PCBs, thyroid function and neurodevelopment.