|
1997
Award Recipients |
| |
Agricultural Pesticide
Use and Its Relationship to Childhood Morbidity
Edward Avol, M.S., Department of Preventive Medicine,
USC, Dr. Rob McConnell, M.D., Department of Preventive
Medicine, USC |
| Abstract:
The goal of this study is to demonstrate the feasibility
of assessing the relationship between pesticide
drift in the rural community of Lompoc and acute
illness in school children. Investigators will link
the USC Children's Health Study school absence database
with a unique California data base of all agricultural
applications of pesticides, geographically referenced
by day, volume, type of application (aerial or ground)
and type of pesticide. Analysis of one year of school
absences for 150 school children, aged 9-10 years,
will be conducted with respect to application of
different classes of pesticides within 1/4, 1/2,
and 1 mile in the previous 24 and 48 hours. The
analysis will use a novel case-crossover statistical
design (developed by the Study Design Research Core)
that compares the health of study subjects on both
days of school-based absence and days of attendance. |
Final Report:
The investigators initially planned to use the computerized
data tapes of the Department of Pesticide Regulation
for their exposure assessment. As these records
are available for the entire state, they are a resource
for the eventual expansion of this pilot project
to examine a large number of schools for absences.
However, this data set specifies exposure only to
the nearest square mile. In addition, because a
farm may overlap two or more square mile quadrants,
but exposure is assigned only to one, the precision
of exposure is poor. While this may be useful for
probabilistic modeling of the likelihood of low
level exposure, as proposed in another pilot project,
it is less useful for estimating acute exposures
of sufficient magnitude to produce acute illness
and school absence. In examining local data in Lompoc,
from which the statewide database is compiled, the
investigators have found records that pinpoint applications
from specific farms in a ¼ square mile grid
of the county. These local data also identify the
means of application (tractor drawn boom, helicopter,
etc), which is an important determinant of the dispersion
of drift and, therefore, the likelihood of exposure.
Based on literature data on dispersion from tractor
drawn boom sprayers, the most common means of application
in Lompoc, the investigators decided that exposures
beyond a ¼ mile radius were likely to be
trivial under most circumstances. Only a single
school in Lompoc was within this distance of any
field. Relatively few applications occurred during
the school year and only some of these were with
pesticides likely to cause acute respiratory symptoms.
The investigators concluded that the electronic
state database of pesticide applications has limited
usefulness for the evaluation of relationships between
exposure and school absences.
|
| |
Assessment of the
Accuracy of Neighborhood Walk Methods to Find the
Addresses of Children Controls
Roberta McKean-Cowdin, post-doctoral student, Bryan
Langholz, Ph.D., Department of Preventive Medicine,
USC |
| Abstract:
A pilot study was completed to assess the feasibility
of using a neighborhood survey to select controls
for a two-stage, prospective study of power line
configuration (wire code) and childhood leukemia.
The proposed control identification technique was
a modified version of the neighborhood walk method
used at the University of Southern California Department
of Preventive Medicine. The purpose of the project
was to determine the size of the neighborhood survey-area
required to identify an adequate pool of potential
controls and to determine if a high neighborhood
response rate could be obtained. Eight neighborhoods
in Los Angeles County were selected and case ages
were assigned to each neighborhood (2-12 years).
Potential controls were defined as those children
who were the same age as the case (± 3 years)
and who resided in the neighborhood blocks adjacent
to, but not in the same block as each case. An 8
hour, counter-clockwise walk was completed around
each case neighborhood. Residents or their neighbors
were asked if an eligible child lived at the address.
Follow-up included a doorstep letter, a mailed survey
letter, follow-up phone call, and a second walk
(for 1 neighborhood). A total of 1,898 households
were surveyed (an average 237 households per neighborhood),
of which 168 included eligible children (246 total
children). The overall percent response for the
survey and follow-up was 70%. Response varied by
neighborhood (54 to 94%). The majority of responses
were obtained directly from the resident (64%).
In a small sub-mailing, 92% of neighbor responses
were validated as accurate by the resident. |
Final Report:
The results of this study show that an adequate
number of potential controls can be identified in
an 8 hours walk period for use in a counter-matched
study of wire code and leukemia. The findings suggest
that neighborhood control selection is a feasible
method of control identification for case-controls
studies when children are matched on age (3 years)
and neighborhood. The counter-matched design has
several advantages over traditional designs used
to study the WC-leukemia association, including:
prospective identification of cases due to increased
power for a small sample size, ability to identify
and evaluate differences in families that choose
to participate from those that choose not to participate
(e.g. WC of house based on street observations),
and collection of detailed covariate histories on
a sub-set of the entire control group.
|
| |
The Influence of
Air Pollution in the Los Angeles Metropolitan Area
on the Occurrence of Birth Defects
Beate Ritz, M.D., Ph.D., Department of Epidemiology,
UCLA School of Public Health |
| Abstract:
The objective of the study is to evaluate whether
birth defects diagnosed in children born to women
who live in the Los Angeles Metropolitan Area and
the South Coast Air Basin (SoCAB) are associated
with elevated levels of 4 criteria air pollutants
(Ozone, NO2 , PM10, CO,) and/or polycyclic hydrocarbons
during the vulnerable period of the first 8-10 weeks
of gestation. Air-pollution, birth-registry, and
birth-defect registry data for the 4 South-Coast
counties (for 1987-1993) are being employed to examine
whether women exposed to increased first-trimester
average pollutant concentrations are more likely
to give birth to malformed children. A geographic
information system has allowed the investigators
to locate the mother's residency near a fixed-site
air monitoring station. Average pollutant levels
are being calculated according to the proximity
of the residency to a fixed-site air-monitoring
station, i.e. each individual birth is being assigned
a first-trimester weekly average level for each
pollutant depending on the recorded zip code of
maternal residency at birth. The investigators are
employing polytomous logistic regression models
using distinct subgroups of birth defects as the
outcome and children born without malformations
comparing their levels of first-trimester pollutants.
A recently developed method helpful for adjustment
for multiple comparisons is being used. |
| Final Report:
Findings from studies previously conducted in Los
Angeles, China, and Brazil and this pilot study
suggest that exposure to ambient air pollution during
pregnancy may cause adverse birth outcomes, such
as low birth weight, preterm birth, and fetal death.
It is unknown whether indoor and in-vehicle air
pollution sources contribute to these outcomes.
This study found that of all the pollutants measured
in the Los Angeles area, ambient CO was the most
consistent and important predictor of low birth
weight (LBW) in term infants. After adjustment for
all confounding factors available on birth certificates
as well as for differences in commuting habits across
areas of monitoring, the investigators found a 22%
increase in LBW [odds ratio (OR) = 1.22; 95% confidence
interval (CI), 1.03-1.44] among the children born
to mothers who were exposed on average to more than
5.5 ppm CO (95th percentile for exposure) during
the last trimester of pregnancy. The excess of LBW
infants rose to 33% for mothers giving birth to
a second or higher order child and to 54% for mothers
under the age of 20 years. However, for the latter
groups, the confidence intervals around the effect
estimate were wide; i.e., there was less statistical
precision due to the decreasing size of the cohort.
Among the offspring of women exposed to CO in the
50-95th-percentile range, the odds of LBW were considerably
smaller, just 2-4% higher than for infants whose
mothers' exposure to CO fell below the median level. |
Publications:
Ritz B, Yu F. The Effect of Ambient Carbon Monoxide
on Low Birth Weight among Children Born in Southern
California between 1989 and 1993. Environ Health
Perspect 1999, 107(1):17-25.
Ritz B, Yu F, Chapa G, Fruin S. Ambient Air Pollution
and Preterm Birth in Southern California, 1989-1993.
Accepted for publication in Epidemiology 1999.
Ritz B, Yu F. The Effect of Ambient Carbon Monoxide
Levels on Birth Weight in Southern California Between
1987 and 1993. J Clin Epidemiol, 1998; 51 (Suppl.1):
S23
Ritz B, Yu F. Ambient Air Pollution and Low Birth
Weight in Southern California 1987-1993. Abstract
Epidemiology 1998, 9 (Suppl 4): S160.
§
Ritz B, Yu F. Ambient Air Pollution and Preterm
Birth in Southern California 1989-1993. Abstract
Epidemiology 1999; 10 (Suppl 4): S126
|
| |
Gene-Tobacco Interactions
in the Etiology of Gastric Cancers
Anna Wu, Ph.D., Department of Preventive Medicine,
USC |
| Abstract:
The main objective of this proposed pilot study
is to use metabolism genes as a tool to determine
whether polycyclic aromatic hydrocarbons (PAHs),
heterocyclic aromatic amines (HAs), and arylamines
from tobacco smoke are human gastric carcinogens.
For this pilot study, the investigators are conducting
genotyping work on five metabolism genes (CYP1A1,
GSTM1, GSTT1, NAT1, and NAT2) on the first 100 Caucasian
gastric cancer patients and an equal number of Caucasian
controls for whom there are questionnaire data and
blood specimens for lymphocytes. The laboratory
work is conducted under the supervision of the Molecular
Biology and Biological Processing Sample Core Director,
Dr. Louis Dubeau. Work to extract DNA is ongoing
and has been completed on 134 of 200 samples. Dr.
Dubeau's laboratory has conducted preliminary genotyping
of GSTM1 and GSTT1 on these 100+ samples. Methods
to genotype CYP1A1, NAT1 and NAT2 are being refined
and tested. All 200 samples will be analyzed for
these 5 metabolism genes. |
Final Report:
In the completed population-based case-control study
of gastric and esophageal adenocarcinomas in Los
Angeles County, the results showed that current
smokers experienced a significant 2-fold increase
risk. The deleterious effect was observed in both
proximal (gastric cardia and esophageal cancers)
and distal gastric cancers although the association
was somewhat stronger for the former group. Despite
the accumulating evidence from epidemiologic studies
that smoking has a causal role in gastric cancer
development, the precise mechanism by which tobacco
smoke induces gastric cancer is not known. This
pilot gastric cancer study aimed to explore whether
polymorphisms in enzyme systems, including glutathione
S-transferases (GST) that are involved in the metabolism
of tobacco carcinogens, may influence the risk of
gastric cancer. Results based on the first 130 cases
and 180 controls showed a 33% increased risk associated
with the GSTM1 null genotype, a 20% increased risk
associated with the GSTT1 null genotype and a 2.5-fold
(95% CI=1.0-6.3) increased risk associated with
null genotype of both genes, after adjustment of
age, sex, ethnicity and smoking in multivariate
analysis. However, the modest sample size did not
allow the investigators to conduct ethnic specific
gene-disease analyses or to investigate the gene-disease
associations stratified by tobacco smoke exposure.
|
| |
Evaluation and Validation
of Environmental Tobacco Smoke Tracers
William Hinds, Sc.D., Department of Environmental
Health Sciences, UCLA |
| Abstract:
This study will use a new system that generates
Environmental Tobacco Smoke (ETS) as mixtures of
exhaled mainstream (MS) and sidestream (SS) smoke,
each generated under realistic smoking conditions.
The research will also improve understanding of
ETS markers in the indoor environment and validate
their ability to estimate ETS mass concentration
using both laboratory and field studies. Environmental
tobacco smoke (ETS) is a complex mixture of sidestream
smoke and exhaled mainstream smoke. Each has different
chemical composition and properties. Estimates of
the fraction of exhaled mainstream smoke in environmental
tobacco smoke range from 10 to 50%. Nevertheless
many studies simulate environmental tobacco smoke
by using only sidestream smoke. The objective of
this study was to evaluate markers that can be used
to identify environmental tobacco smoke and to distinguish
exhaled mainstream smoke from sidestream smoke in
environmental tobacco smoke. This cannot be calculated
with acceptable accuracy because of the uncertainty
as to the deposition fraction of mainstream smoke. |
| Final Report:
In the evaluation of properties of exhaled mainstream
smoke and sidestream smoke the investigators found
that, after release into the ambient environment,
aged exhaled mainstream smoke particles have a larger
size distribution than that for sidestream smoke
particles. This is the first observation of the
bimodal size distribution in environmental tobacco
smoke due to the distinct modes from exhaled mainstream
smoke and sidestream smoke. Two publications have
resulted from this pilot project grant. The first
is a presentation at the 1997 annual meeting of
the American Association for Aerosol Research and
the second is a chapter in Ms Kadrichu's Ph.D. thesis.
A paper is in preparation on these results and is
scheduled for completion in mid-2000. The investigator
plans to submit a proposal to the UC Tobacco-Related
Disease Research Program to follow-up on these findings. |
Publications:
Kadrichu NP, Hinds WC. A new generation system for
Environmental Tobacco Smoke. Sixteenth annual conference
of the AAAR, October 13-17, 1997, Denver, CO (1997)
(abstract).
Kadrichu NP. Cigarette Smoke and Environmental Tobacco
Smoke: Generation, Particle Dynamics, and Size Characterization.
(Chapter 4, Exhaled Mainstream Smoke Contribution
to Environmental Tobacco Smoke) Ph.D. Thesis, UCLA
(1998).
|
| |
Analysis of the
Mutagenic Potential of Gasoline Fuel Additives Using
Ames Bacterial Tester Strains and Mammalian Cell
Mutagenicity Assays
Colin Hill, Ph.D., Paul Spears, M.D., George Olah,
Ph.D., Department of Radiation Oncology, USC |
| Abstract:
Methyl tert-butyl ether (MTBE) is an oxygenate widely
used in the United States as a motor vehicle fuel
additive to reduce emissions and as an octane booster.
But it is the potential for MTBE to enter drinking
water supplies that has become an area of public
concern. MTBE has been shown to induce liver and
kidney tumors in rodents but the biochemical process
leading to carcinogenesis is unknown. MTBE was previously
shown to be non-mutagenic in the standard Ames plate
incorporation test with tester strains that detect
frame shift (TA98) and point mutations (TA100) and
in a suspension assay using TA104, a strain that
detects oxidative damage, suggesting a non-genotoxic
mechanism accounts for its carcinogenic potential.
These strains are deficient in excision repair due
to deletion of the uvrB gene. The investigators
hypothesized that the carcinogenic activity of MTBE
may be dependent upon a functional excision repair
system that attempts to remove alkyl adducts and/or
oxidative base damage caused by direct interaction
of MTBE with DNA or by its metabolites, formaldehyde
and tert-butyl alcohol (TBA), established carcinogens
that are mutagenic in some Ames strains. To test
the hypothesis, the genotoxicity of MTBE-induced
DNA alterations was assayed using the standard Ames
test with TA102, a strain similar to TA104 in the
damage it detects but uvrB+ and therefore excision
repair proficient. The assay was performed 1) with
and without Aroclor-induced rat S-9, 2) with and
without the addition of formaldehyde dehydrogenase
(FDH), and 3) with human S-9 homogenate. |
| Final Report:
MTBE was weakly mutagenic when tested directly and
moderately mutagenic with S-9 activation producing
between 80-200 TA102 revertants/mg of compound.
Mutagenicity was inhibited 25-30% by FDH. TA102
revertants were also induced by TBA and by MTBE
when human S-9 was substituted for rat S-9. The
investigators conclude that MTBE and its metabolites
induce a mutagenic pathway involving oxidation of
DNA bases and an intact repair system. As a result
of the study Dr. Hill was invited to present the
data at the GETA meeting held at EPRI in Palo Alto
in the fall of 1998. Additionally, this study and
others have led to new regulations on MTBE use in
California and recently Governor Gray Davis signed
legislation for the gradual elimination of MTBE
from gasoline in California because of its toxic
and carcinogenic potential. |
Publications:
Williams-Hill D, Spears CP, Prakash S, Olah GA,
Shamma T, Moin T, Kim LY, Hill CK. Mutagenicity
studies of methyl-tert--butylether using the Ames
tester strain TA102. Mutation Research 1999, 446:15-21.
|
| |
Arsenic Induced
Carcinogenesis: A Murine Model for the Induction
of Cancer in Methyl-Deficient C57BL/6 Mice
John Froines, Ph.D., Department of Environmental
Health Sciences, UCLA |
| Abstract:
Arsenic is an established human carcinogen. The
mechanistic pathway by which arsenic causes cancer
is not understood. In preparation for a 24-month
chronic study assessing cancer in methyl-deficient
male C57BL/6 mice, a 130-day subchronic study of
sodium arsenite was undertaken to establish baseline
toxicity data. Mice were administered arsenic via
drinking water at 0, 2.6, 4.3, 9.5 or 14.6 mg sodium
arsenite/kg/day. Dosing continued 7 days a week
for the length of the study. Deaths of 3 of the
control animals (methyl-sufficient/no arsenic) at
Day 111 of the study did not appear to be compound-related.
The death of a single animal in the high-dose group
did appear to be treatment-dependent. |
| Final Report:
A dose-related reduction was observed for liver
weight. Mild to severe fatty infiltration was observed
in the livers of methyl-deficient/arsenic treated
animals. Severe liver damage was noted in 2 animals
from the 2.6 and 4.3 mg/kg/day groups. In addition,
hypertrophy/hyperplasia of the bladder epithelium
was found in 43/60 mice treated with sodium arsenite.
No histopathological changes were evident in any
other tissue examined. The no observed effect level
(NOEL) and no observed adverse effect level (NOAEL)
of this study could not be determined as the lowest
dose administered produced adverse effects. The
maximum tolerated dose (MTD) for animals maintained
on methyl-deficient diets was 2.6 mg/kg/day. |
Publications:
Arsenic Induced Carcinogenesis: Perturbations in
p53 and Ha-ras methylation patterns. (Poster Presentation)
Toxic Substances Research and Teaching Program (TSR&TP),
12th Annual Research Symposium, April 1999.
Arsenic Induced Carcinogenesis: A murine model for
the induction of cancer in methyl-deficient C57Bl/6J
mice. (Poster Presentation) Toxic Substances Research
and Teaching Program (TSR&TP), 11th Annual Research
Symposium, April 1998.
Arsenic Induced Carcinogenesis: A murine model for
the induction of cancer in methyl-deficient C57Bl/6J
mice. (Poster Presentation) International Conference
on the Health Effects of Arsenic, June 1997, 1998.
and 1993. Environmental Health Perspectives 1999,
107(1):17-25.
Okoji R S, Hernandez A, Leininger J, Froines JR.
Subchronic Study of Sodium Arsenite in Methyl-Deficient
Male C57BL/6 Mice. (Document in press) |
| |
|
 |
