Mold in Maize Less Exposure May Mean Less Cancer

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http://www.ehponline.org/docs/2001/109-3/ss.html

Mold in Maize

Less Exposure May Mean Less Cancer

Mold-produced toxins have tainted food crops probably since the

beginnings of agriculture. These mycotoxins can occur when certain

molds infect food crops before or after harvest. Both humans and

animals are vulnerable to poisoning through consumption of

contaminated foods, with acute or chronic illness--including cancer--a

potential result. A study by K. Chelule of the University of

Natal in Durban, South Africa, and colleagues focuses on the link

between exposure to fumonisin B1, a mycotoxin produced by Fusarium

verticillioides, and risk of esophageal cancer [EHP 109:253-256].

In the 1980s, researchers from the Medical Research Council of South

Africa discovered a highly suggestive link between esophageal cancer

and exposure to fumonisin B1. Because F. verticillioides infects

maize, a staple crop throughout the world, large populations may be

exposed to fumonisin B1. The work initiated in the 1980s focused on

the high incidence of esophageal cancer in certain districts of the

Transkei region of South Africa. A key difference between these

districts and control areas was that maize in the areas with high

cancer rates was highly contaminated with fumonisin B1. Similar

observations were later made elsewhere, notably in China.

Corn

Unsavory stew. Exposure to mold-produced toxins in staple crops

such as maize raises the risk of esophageal cancer.

Photo credit: s Hopkins University EHSC

The study by Chelule and colleagues looks at fumonisin B1 exposure

among urban and rural populations in KwaZulu Natal province. The

researchers wanted to see how fumonisin B1 exposure among people of

KwaZulu Natal compares to that of the Transkei populations, which

could indicate whether their potential risk for esophageal cancer is

as high. The researchers conclude that the KwaZulu Natal populations

encounter lower levels of fumonisin B1 contamination overall, although

rural people have a greater risk of exposure than urban ones.

Eighty-four people took part in the study, 44 from the Durban

metropolitan area and 40 from the Tugela Valley, a rural area about

200 kilometers north of Durban. The researchers collected samples of

unprocessed maize and sorghum from each person's home, as well as

prepared foods including phutu (cooked milled maize), amahewu (a

nonalcoholic fermented gruel-like drink made from maize), and isizulu

(an alcoholic fermented drink made from maize and sorghum). Fecal

samples were also collected from study participants.

The differences observed between unprocessed rural and urban maize

samples were significant. Not only were a higher percentage of rural

samples contaminated (32% compared to 6%), but the level of

contamination was also greater, as determined by chemically extracting

fumonisin B1 from the food and drink samples and analyzing the

quantity extracted. This finding translates to the rural population

having a 6 times higher risk of fumonisin B1 exposure--and potential

consequences--than the urban population, say the researchers. However,

they note that even the highest mycotoxin level found in this study,

22.2 milligrams per kilogram of grain, falls far short of that

measured in the Transkei study, which exceeded 117 milligrams per

kilogram. None of the sorghum samples from either urban or rural areas

contained detectable amounts of fumonisin B1, and among the cooked

foods only rural phutu was contaminated. Of the rural fecal samples,

33% had measurable amounts of fumonisin B1 as compared to 7% of the

urban samples. The researchers note that fecal analysis provides a

useful short-term indicator for fumonisin B1 exposure.

The researchers conclude that the people of KwaZulu Natal have a lower

risk of fumonisin B1 exposure and the potentially related esophageal

cancer than the people of Transkei. They attribute urban-rural

differences in this study to a more varied diet and greater likelihood

of food safety regulations in urban areas. Further, given that sorghum

is less prone to contamination, they suggest that their results might

encourage cultivating sorghum rather than maize in the Tugela Valley.

However, they caution that further study is necessary before taking

such a step. - R. Barrett

Arsenic and Endocrines

New Study Suggests Disruption

Chronic low-level human exposure to arsenic is associated with

increased cancer risk. Epidemiologic studies of exposed populations in

Asia and South America have shown a significant increase in the risk

of skin, lung, liver, and bladder cancers, yet arsenic's carcinogenic

mechanism remains unknown. Chronic exposure to arsenic also is

associated with elevated risks of type 2 diabetes mellitus and

vascular disease. In this issue, Kaltreider, Hamilton,

and colleagues from Dartmouth Medical School in Hanover, New

Hampshire, may have uncovered a clue to a central mechanism behind

arsenic's myriad adverse health effects [EHP 109:245-251].

Low-level exposure to arsenic in drinking water is widespread in the

United States and elsewhere. In New Hampshire, for instance, where 40%

of the population's water supply comes from private wells, as much as

8% of the state (one-fifth of all private well users) may be exposed

to arsenic concentrations between the U.S. Environmental Protection

Agency's proposed standard of 10 parts per billion and the current

standard of 50 parts per billion. At industrial sites and toxic waste

sites--including over 70% of all Superfund waste sites--arsenic is

usually found in combination with many other toxic chemicals, and it

can leach into groundwater and find its way into drinking water.

The current study follows up on previous research that found that

arsenic affects expression of the well-characterized

phosphoenolpyruvate carboxykinase gene in rat liver cancer cells,

reducing its responsiveness to hormone signals. Working in Hamilton's

laboratory, which studies the effects of toxic metals on gene

expression, Kaltreider and colleagues studied three sets of rat liver

cancer cells. The first set was treated with various noncytotoxic

concentrations of arsenite solution. The second was treated with a

synthetic glucocorticoid hormone called dexamethasone (Dex). The third

was treated with both arsenite and Dex. Glucocorticoids mediate a

large array of effects. Among them are blood glucose regulation,

vascular function, cell differentiation, and apoptosis, all of which

are key functions in systems affected by arsenic exposure.

The researchers found that low doses of arsenic blocked the

glucocorticoid receptor (GR) from responding to its normal hormone

signal. More specifically, the researchers found that arsenic

selectively disrupted the ability of GR in exposed cells to regulate

the expression of its target genes in the nucleus, with the highest

arsenite dose causing a greater than 50% suppression in Dex-inducible

expression. Arsenite did not appear to interfere with the binding of

Dex to GR or with the ability of Dex to activate GR and cause it to

migrate to the nucleus. However, once inside the nucleus GR was unable

to stimulate gene expression, even though it was fully activated by

Dex.

Arsenic thus appears to act as a new class of endocrine disruptor by

altering certain aspects of receptor function, even in nontoxic doses.

GR is a critical player in mediating blood glucose regulation, so

disrupting that function could be a part of how arsenic affects

diabetes. GR is also an important regulator of normal vascular

function, so disrupting GR in these tissues may contribute to how

arsenic causes vascular disease. Finally, GR has been shown in animal

and cell culture studies to play a crucial role in the cancer process

in both the skin and the lung--both of which are targets for

arsenic-induced carcinogenesis--and loss of GR function in animal

tumor models has been shown to promote the cancer process in both

tissues. The researchers therefore theorize that arsenic's action as

an endocrine disruptor, although perhaps not the only mechanism, may

be an important contributing factor in several different

arsenic-related diseases.

Arsenic's effects also seem to be highly specific for GR-induced gene

expression. Kaltreider and colleagues are currently investigating

whether binding of arsenic to GR directly causes the alterations in GR

function. They suggest that possible effects of arsenic on other

steroid receptors such as those for estrogen and progesterone should

be investigated to determine whether arsenic's effects are specific to

GR or a general effect on this family of hormone receptors. -n

phson

From Animal Feed to People Food

The Belgian Dioxin Incident

In January 1999, animal feedlots in Belgium were contaminated with

polychlorinated biphenyls (PCBs) and dioxins including polychlorinated

dibenzo-p-dioxins and polychlorinated dibenzofurans. The dioxins,

probably originating from oil left at a waste recycling center,

entered the food supply via animal feed made with recycled animal fat.

(In Belgium, waste fat from recycling centers is commonly mixed with

fat from slaughterhouses to make animal feed.) Five hundred tons of

the contaminated feed was distributed to farms, mostly poultry

operations, throughout Belgium. In this issue, Nik van Larebeke and

colleagues from four Flemish universities conclude that the incident

may have doubled or tripled the PCB/dioxin body burden of some

Belgians [EHP 109:265-273].

News of the incident broke in late May, sparking a public outcry and a

scramble by government agencies to assess the human health damage. The

Ministries of Public Health and Agriculture ordered testing of over

20,000 samples of beef, pork, poultry, eggs, milk, and fat-containing

processed foods found on Belgian grocery shelves. The sampling,

conducted between May and August 1999, analyzed the health impact of

the contaminants on consumers and provided the materials for the

current study.

cows How now, cow chow? PCBs and dioxins taken up by livestock that

ate contaminated feed may have doubled or tripled the PCB/dioxin body

burden of some Belgians.

Photo credit: PhotoDisc

Dioxins, a group of chemical compounds released by processes such as

waste incineration and the burning of household fuel, have been linked

to health effects ranging from skin disease to cancer. PCBs are

mixtures of synthetic organic chemicals. Like dioxins, PCBs have been

linked to cancer; they have also been associated with neurotoxicity,

reproductive and developmental toxicity, immune suppression, liver

damage, skin irritation, and endocrine disruption.

Van Larebeke and colleagues sorted the food samples into three

categories: those traceable to farms that used contaminated feed,

those traceable to farms that did not use contaminated feed, and those

for which a link with the contamination incident could not be clearly

established. The sampling effort by 23 labs measured dioxins with mass

spectrometry and quantified PCBs using gas chromatographic techniques

along with electron capture or mass spectrometry.

Compared with dioxin incidents elsewhere, the Belgian incident exposed

more people but to much smaller amounts of dioxins. The analysis

suggests that in terms of added cancer risk, the incident could result

in 32-1,540 additional cancer deaths over the projected lifetime of

the total Belgian population of 10 million, and PCB exposure could add

between 22 and 6,545 cancer deaths. These ranges are based on applying

two different risk estimates for lifetime exposure to the amount of

contaminants in the incident exposure.

Depending on a person's diet and the chance occurrence of high levels

of contamination, however, the effects could be much more serious. The

potential impacts of three common dietary patterns typical of the

average Belgian citizen were assessed. One pattern assumed the

ingestion of 15 grams of heavily contaminated animal fat per day and

resulted in a 75% increase in dioxin body burden. Another assumed the

ingestion of three portions of heavily contaminated chicken meat per

week and resulted in a 42% increase in dioxin body burden. A third

common dietary pattern resulted in a 48% increase in dioxin body

burden. Some people may have incurred even higher exposures because

consumption of products such as milk and derived food items such as

sauces and pastries were not factored in to the estimations.

The 1999 Belgian dioxin incident added further risk to background

levels that were already high. The authors warn that significant

numbers of Belgians who consumed contaminated products temporarily

increased their intake of dioxins to a level up to 100 times greater

than that recommended by the World Health Organization. Furthermore,

conclude the authors, the long-term effects may be particularly hard

to detect because of the high background levels. The researchers

recommend further monitoring of exposed populations and stricter

chemical and physical hygiene, including better screening of materials

left at recycling centers. - A.