Arsenic Research
Reprint from NIEHS news letter
International Arsenic Research Program
(Allan Smith, Mary Lou Biggs & Craig Steinmaus)
Center member Professor Allan Smith first became interested in the effects of naturally occurring arsenic in drinking
water after being asked by the California Department of Health Services to consider potential cancer risks surrounding
the current U.S. arsenic drinking water standard of 50 micrograms per liter. At the time, it was well known that
arsenic in drinking water could cause pigmentation of the skin, small raised keratotic lesions on the palms and
soles, as well as skin cancer. However, based on studies from Taiwan, it was becoming increasingly apparent that
arsenic could also cause fatal cancers such as bladder and lung cancer. A linear risk extrapolation from Taiwan
to U.S. drinking water levels raised the possibility that consuming water containing 50 micrograms arsenic/L (the
drinking U.S. water standard) might result in 1 of 100 persons dying from arsenic caused cancer.
To confirm the Taiwan results, Dr. Smith and his research team searched for other highly exposed populations. This
first led to Argentina, where the people of the Province of Cordoba were found to have high rates of skin diseases
caused by drinking water from arsenic contaminated wells. The research team subsequently found increased mortality
rates of both bladder and lung cancer in the region, especially in the most highly exposed areas where arsenic
levels averaged close to 200 micrograms/L.
Even more striking were the results from a second mortality investigation, this one in a remote desert area in
northern Chile, where use of drinking water with arsenic levels as high as 1000 micrograms/L began in the 1950s.
The research team found bladder cancer mortality rates seven times higher than the rest of Chile, and lung cancer
mortality rates also markedly above national levels. As in the Argentina study, smoking could be ruled out as an
explanation since the rates of other pulmonary diseases in this region were normal. The research team reached the
conclusion that naturally occurring arsenic in drinking water in Northern Chile, had been a more important cause
of mortality than cigarette smoking.
Additional studies by the research team investigated dose-response and susceptibility issues and the potential
effects of arsenic at levels found in the United States. One set of studies investigated the role of methylation,
which is thought to be the body's natural mechanism to protect itself from arsenic. It had been suggested that
at low doses of arsenic the body has sufficient capacity to fully methylate and thereby inactivate all the inorganic
arsenic it encounters. However, analysis of urine samples from studies in Nevada and Chile by collaborator Professor
David Kalman from the NIEHS Center at the University of Washington suggested otherwise. Inorganic arsenic was present
in urine even at low levels of arsenic intake in drinking water, implying incomplete methylation and no assurance
of protection even at low exposures.
|
| Cancer mortality in Region II of Chile, which had high levels of arsenic in drinking water, compared to the
rest of the country, showing 6- to 8-fold increases in bladder cancer mortality, as well as increases in lung,
kidney and skin cancer mortality. The lack of increase in deaths from chronic obstructive pulmonary disease (COPD)
was part of the evidence that smoking was not involved in the increased cancer risks. |
A parallel set of studies, done in collaboration with Center Member and Superfund Program Director, Professor
Martyn Smith, involved collecting bladder cells from people drinking arsenic-contaminated water in Nevada and Chile.
The results provided evidence that those with high levels of arsenic in their water have an increased proportion
of bladder cells with genetic damage. Furthermore, these changes were detected in study participants with arsenic
levels equivalent to those commonly found in people in the United States. Additionally, when 40 of the highly exposed
households in the Chile study were supplied with low-arsenic water (less than 50 micrograms/L) for a period of
two months, there was a decrease in the number of people showing damage to bladder cells.
Currently, Dr. Allan Smith and his research team are involved in a number of other studies of arsenic health effects.
In collaboration with local scientists, they are conducting a study of bladder cancer patients and healthy individuals
in arsenic-exposed areas of Argentina and Chile. Researcher Mary Lou Biggs is supervising the fieldwork, which
consists of interviews, collection of biological specimens, and determination of arsenic levels in drinking water
sources. Additionally, post-doctoral fellow Dr. Lee Moore, in collaboration with Dr. Fred Waldman of the University
of California, San Francisco, School of Medicine, is examining genetic changes in tumors from these bladder cancer
patients in order determine the mechanism by which arsenic causes cancer. Dr. John Weincke, also at UCSF, is analyzing
DNA from normal tissue of participants to see if certain genes can influence susceptibility to arsenic-caused cancer.
|
