1
ization has many effects on birds, and it remains to be seen how noise ranks among them. —S. MILIUS Tiny Labs Polymers on silicon chip catch, release proteins Using polymers as tiny molecule-absorbing sponges, researchers have taken a step toward shrinking room-size chemical labo- ratories to the size of a crumb. Microchips full of tiny channels and mixing chambers may eventually enable scientists to analyze minute amounts of any solution quickly and accurately (SN: 8/15/98, p. 104). Such so-called laborato- ries-on-a-chip could be use- ful for detecting the first molecular signs of disease in a blood sample or the pres- ence of a bioterrorism agent in the environment. For the technology to work, however, it has to manipulate molecules to be analyzed on the chip. Toward that end, researchers at San- dia National Laboratories in Albuquerque have developed a new method for gently grabbing and releasing pro- teins at particular places on a silicon wafer. This system could be used to concentrate biological mol- ecules from dilute solutions for analysis, says Bruce C. Bunker. He and his Sandia colleagues describe their research in the July 18 Science. The investigators started with a silicon wafer on which they’d applied a silicon nitride coating, says team member Dale L. Huber. After etching a nar- row channel in the silicon, the scientists deposited thin gold lines on top of the nitride layer so that the lines formed bridges over the silicon nitride–covered trench. Because the trench acts as an insulator, each gold bridge can be electri- cally heated. Each is essen- tially “a microtoaster,” says Bunker. Finally, the researchers grew a dense thicket of polymer molecules into a thin film over the gold lines. At 35°C, about body temperature, the polymer switches from a water-attracting state to a water-repelling one. When the researchers introduce a couple of micro- liters of protein-containing solution to the SCIENCE NEWS 38 JULY 19, 2003 VOL. 164 SCIENCE NEWS This Week SCIENCE T race amounts of cadmium can mimic estrogen’s effects on cells and alter the reproductive system of female rats, a new study shows. The finding may expand the rap sheet on cadmium— already fingered in lung cancer and kidney damage—to include reproductive disorders and pos- sibly hormone-related malig- nancies such as breast cancer. Meanwhile, a separate report reveals that cadmium also disrupts DNA repair inside cells, offering an explanation for its cancer-causing effects in cigarette smoke and industrial pollution. Cadmium is a white metal used in alloys, batteries, metal coatings, and pigments. In the August Nature Medi- cine, molecular biologist Mary Beth Martin of Georgetown University in Washington, D.C., and her colleagues report that female rats injected with cad- mium chloride grew thicker uterine linings and larger mammary glands, effects that mirror the animals’ normal responses to an estrogen boost. These changes arose even though the rats had had their ovaries removed and so were making none of their own estrogen. The findings validate earlier cell-culture studies showing that cadmium binds to a receptor molecule on cells that normally binds estrogen. When the metal does so, it sets off a genetic chain reaction and growth processes similar to those induced by the hormone itself, Martin says. The rats also showed evi- dence of extra amounts of two proteins typically activated by estrogen—the progesterone receptor protein and C3, an immune system protein. Revealing another estrogen- mimicking effect, cadmium- exposed female rats with intact ovaries bore female pups that gained weight quicker than usual and reached puberty ear- lier than normal. The rat findings indicate that cadmium can rev up unwanted cell growth by mimicking estrogen, says Martin. Her group is planning experiments to determine whether such an endocrine disruption by cad- mium may be a cause of breast cancer. In the other new study, researchers found that low concentrations of cadmium cause an extremely high rate of genetic mutation in yeast. But rather than damage DNA directly, the metal appears to cause mutations by inhibiting a cell’s DNA-repair mechanism. Normally in any organism, some cells die off naturally and others multiply to take their places. However, errors com- monly arise in this replication process, which is why DNA has built-in repair mechanisms. Among them is DNA-mismatch repair, a mutation-avoidance system that suppresses tumor formation, says study coauthor Dmitry A. Gordenin, a geneti- cist at the National Institute of Environmental Health Sciences in Research Triangle Park, N.C. However, in yeast cells exposed to cadmium, this DNA-repair process goes awry. Cadmium exposure pushed the mutation rate up as much as 2,000-fold in these cells, Gordenin says. DNA-mismatch repair is guided by specific genes and the proteins they encode. In the July Nature Genetics, Gor- denin and his colleagues say they don’t know which pro- teins are affected by cadmium but that the evidence of muta- tions is unmistakable. Cadmium is present in soil and therefore in many foods. In people, it lingers in the body for decades, tending to accumulate in the kidneys, liver, lungs, and prostate. Once inside a person, it binds chemically to certain mole- cules in tissues and so isn’t readily excreted. Cadmium is one of the major contaminants of tobacco smoke, says Gordenin. “Smokers definitely accumu- late more cadmium in their lungs” than nonsmokers do, he says, and the new research suggests one of the mecha- nisms by which smoking leads to lung cancer. These studies are “both extremely important steps in [determining] cadmium’s role in the human body,” says John A. McLachlan of Tulane Uni- versity in New Orleans. They add to a growing body of knowledge about pollutants that mimic hormones and thus have an impact on health, he says. —N. SEPPA Metal’s Mayhem Cadmium mimics estrogen’s effects, thwarts DNA repair PROTEIN HOT SPOT Each dark bar in the white area of this microchip is a polymer- covered gold bridge that can be heated. Doing so can concentrate protein from a solution applied to the chip.

Tiny labs: Polymers on silicon chip catch, release proteins

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Page 1: Tiny labs: Polymers on silicon chip catch, release proteins

ization has many effects on birds, and itremains to be seen how noise ranksamong them. —S. MILIUS

Tiny LabsPolymers on silicon chipcatch, release proteins

Using polymers as tiny molecule-absorbingsponges, researchers have taken a steptoward shrinking room-size chemical labo-ratories to the size of a crumb.

Microchips full of tiny channels andmixing chambers may eventually enable

scientists to analyze minute amounts ofany solution quickly and accurately (SN:8/15/98, p. 104). Such so-called laborato-ries-on-a-chip could be use-ful for detecting the firstmolecular signs of disease ina blood sample or the pres-ence of a bioterrorism agentin the environment.

For the technology towork, however, it has tomanipulate molecules to beanalyzed on the chip. Towardthat end, researchers at San-dia National Laboratories inAlbuquerque have developeda new method for gentlygrabbing and releasing pro-teins at particular places ona silicon wafer. This systemcould be used to concentrate biological mol-ecules from dilute solutions for analysis,says Bruce C. Bunker.

He and his Sandia colleagues describetheir research in the July 18 Science.

The investigators started with a siliconwafer on which they’d applied a siliconnitride coating, says team member Dale L.

Huber. After etching a nar-row channel in the silicon,the scientists depositedthin gold lines on top of thenitride layer so that thelines formed bridges overthe silicon nitride–coveredtrench. Because the trenchacts as an insulator, eachgold bridge can be electri-cally heated. Each is essen-tially “a microtoaster,” saysBunker.

Finally, the researchersgrew a dense thicket ofpolymer molecules into athin film over the gold

lines. At 35°C, about body temperature, thepolymer switches from a water-attractingstate to a water-repelling one. When theresearchers introduce a couple of micro-liters of protein-containing solution to the

S C I E N C E N E W S3 8 J U LY 1 9 , 2 0 0 3 V O L . 1 6 4

SCIENCENEWSThis Week

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Trace amounts of cadmiumcan mimic estrogen’seffects on cells and alter

the reproductive system offemale rats, a new studyshows. The finding may expandthe rap sheet on cadmium—already fingered in lung cancerand kidney damage—to includereproductive disorders and pos-sibly hormone-related malig-nancies such as breast cancer.

Meanwhile, a separatereport reveals that cadmiumalso disrupts DNA repair insidecells, offering an explanationfor its cancer-causing effects incigarette smoke and industrialpollution. Cadmium is a whitemetal used in alloys, batteries,metal coatings, and pigments.

In the August Nature Medi-cine, molecular biologist MaryBeth Martin of GeorgetownUniversity in Washington, D.C.,and her colleagues report thatfemale rats injected with cad-mium chloride grew thickeruterine linings and largermammary glands, effects thatmirror the animals’ normalresponses to an estrogenboost. These changes aroseeven though the rats had hadtheir ovaries removed and so

were making none of theirown estrogen.

The findings validate earliercell-culture studies showingthat cadmium binds to areceptor molecule on cells thatnormally binds estrogen. Whenthe metal does so, it sets off agenetic chain reaction andgrowth processes similar tothose induced by the hormoneitself, Martin says.

The rats also showed evi-dence of extra amounts of twoproteins typically activated byestrogen—the progesteronereceptor protein and C3, animmune system protein.

Revealing another estrogen-mimicking effect, cadmium-exposed female rats with intactovaries bore female pups thatgained weight quicker thanusual and reached puberty ear-lier than normal.

The rat findings indicate thatcadmium can rev up unwantedcell growth by mimickingestrogen, says Martin. Hergroup is planning experimentsto determine whether such anendocrine disruption by cad-mium may be a cause ofbreast cancer.

In the other new study,

researchers found that lowconcentrations of cadmiumcause an extremely high rateof genetic mutation in yeast.But rather than damage DNAdirectly, the metal appears tocause mutations by inhibiting acell’s DNA-repair mechanism.

Normally in any organism,some cells die off naturally andothers multiply to take theirplaces. However, errors com-monly arise in this replicationprocess, which is why DNA hasbuilt-in repair mechanisms.Among them is DNA-mismatchrepair, a mutation-avoidancesystem that suppresses tumorformation, says study coauthorDmitry A. Gordenin, a geneti-cist at the National Institute ofEnvironmental Health Sciencesin Research Triangle Park, N.C.

However, in yeast cellsexposed to cadmium, thisDNA-repair process goes awry.Cadmium exposure pushedthe mutation rate up as muchas 2,000-fold in these cells,Gordenin says.

DNA-mismatch repair isguided by specific genes andthe proteins they encode. Inthe July Nature Genetics, Gor-denin and his colleagues say

they don’t know which pro-teins are affected by cadmiumbut that the evidence of muta-tions is unmistakable.

Cadmium is present in soiland therefore in many foods.In people, it lingers in thebody for decades, tending toaccumulate in the kidneys,liver, lungs, and prostate. Onceinside a person, it bindschemically to certain mole-cules in tissues and so isn’treadily excreted.

Cadmium is one of themajor contaminants oftobacco smoke, says Gordenin.“Smokers definitely accumu-late more cadmium in theirlungs” than nonsmokers do, hesays, and the new researchsuggests one of the mecha-nisms by which smoking leadsto lung cancer.

These studies are “bothextremely important steps in[determining] cadmium’s rolein the human body,” says JohnA. McLachlan of Tulane Uni-versity in New Orleans. Theyadd to a growing body ofknowledge about pollutantsthat mimic hormones andthus have an impact onhealth, he says. —N. SEPPA

Metal’s MayhemCadmium mimics estrogen’s effects, thwarts DNA repair

PROTEIN HOT SPOT Eachdark bar in the white area ofthis microchip is a polymer-covered gold bridge that canbe heated. Doing so canconcentrate protein from asolution applied to the chip.

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