|Science News, “that there may be a natural function of the [keyless] Ah-receptor complex in regulating normal gene expression in cells.” |
Gasiewicz cautions, however, that the Ah receptor’s dark sides shouldn’t be forgotten. For example, he says that his recent work suggests that the Ah receptor may serve as “one of the body’s master switches” for turning on genes “that transform compounds in cigarette smoke into more toxic chemicals.”
He incubated human cells with extracts of cigarette smoke and then scanned the cells for fragments called micronuclei, which are evidence of precancerous genetic changes. Cells engineered to lack the Ah receptor produced few such micronuclei, while those with the receptor made many.
Then, his team exposed mice—both normal ones and knockout mice lacking the Ah receptor—to cigarette smoke. In the November 1998 Carcinogenesis, his team reported that the normal mice developed many of the micronuclei, indicating gene damage, while the knockouts exhibited none. Exposure to TCDD further increased the number of micronuclei in normal animals exposed to smoke. Says Gasiewicz, “They got a double whammy.”
Taken together, these studies are teasing out new roles—and respect—for the long-dreaded Ah receptor. The most unexpected dividends of Ah-receptor understanding may emerge in medicine. Delineating what compounds trigger the receptor, and when, may lead to more effective cancer therapies (see sidebar). Gasiewicz’s team is also investigating the prospect of engineering drugs to block Ah-receptor activity. They might limit toxicity in smokers or people accidentally exposed to TCDD.
“We might even be able to achieve some of this protection naturally” by, for instance, eating more vegetables like broccoli, Gasiewicz says. “But we can’t hope to do that without a better understanding of this receptor.” n
The old idea that a dioxinlike compound has to be a two-ring, planar molecule—like the dioxin, furan, and PCB shown in the top row—is giving way to a more general description. Most known functional dioxins have at least two rings—usually containing nitrogen—and dissolve readily in lipids. However, even this portrayal may need amending. For instance, at least one single-ringed compound, diaminotoluene, can activate the receptor.
Tapping dioxins as anticancer drugs
Researchers have linked diets rich in brassicas—such as cabbage, broccoli, and brussels sprouts—to a reduced risk of cancer (SN: 9/20/97, p. 183). During their digestion in the gut, these foods produce indole-3 carbinol (I3C), a compound that may prove useful in fighting cancers (SN: 7/3/93, p. 10).
Seven years ago, Christopher A. Bradfield, then at Northwestern University, showed that I3C activates the Ah receptor.
“The gastrointestinal tract is a little chemical manufacturing plant, where microbes are pumping out products like crazy,” Bradfield observes. It makes sense, he says, that the gut would have proteins on hand to detoxify and dispose of any druglike chemicals that intestinal bacteria might brew up from the foods people eat.
Stephen Safe of Texas A&M University in College Station has been probing I3C’s anticancer activity. In the gut, pairs of I3C molecules form a stable structure that can bind to the Ah receptor. “When we give this compound to rats with small mammary tumors,” he says, “the tumors stop growing.”
In the October 1998 Carcinogenesis, he reports evidence that this is an Ah-receptormediated process. “Now we’re developing a whole series of analogs of this vegetable-derived Ah-receptor activator for the treatment of breast cancer,” he says.
So far, Safe has patented two such chemicals, which he and his colleagues are testing in animals. “Both inhibit tumor growth and appear nontoxic,” he says. The new chemicals have no estrogenlike activity, he adds, an important trait for drugs targeted against cancers that use estrogen to fuel their growth. —J. Raloff
A breakdown product of broccoli and related vegetables is serving as a model for novel anticancer drugs that may work through the Ah receptor.
Scientists at the University of Rochester have developed a blue staining technique to highlight cells whose Ah receptors have been turned on. Here, the triggered cells reside in the genitalia of a fetal mouse whose mother was given a nontoxic dose of the dioxin TCDD 24 hours earlier, 1 week before birth. Researchers have known that a developing rodent’s genitals are a target for TCDD toxicity. This staining is the first step in identifying which cells are affected and when.
Cuckoos beg doggedly to trick hosts
Cuckoos are practiced in the art of deception. Once a clandestinely laid cuckoo egg hatches in a reed warbler nest, the chick evicts its native nestmates. The parents, as if feeding their own feathers and blood, tend to the baby cuckoo until it grows larger than both of them together and finally flies away.
Researchers have decoded how one cuckoo elicits the same feeding behavior as a nestful of hatchlings. Rebecca M. Kilner of the University of Cambridge in England and her colleagues determined that baby reed warblers signal the degree of their hunger in two ways—wide-open beaks and persistent calling. Parent warblers, they found, respond to the combination of these signals and feed their young accordingly.
The researchers then examined how the cuckoo manages “a bit of bait and switch,” as Douglas W. Mock of the University of Oklahoma in Norman says in a commentary accompanying the Feb. 25 Nature report. The cuckoo, with its single gaping beak, cannot duplicate the visual pull of a throng of baby warbler beaks, so it tugs at the parents’ other heartstring. The baby cuckoo calls so persistently and rapidly that it sounds like a brood of eight hungry warbler chicks. The din compensates for the cuckoo’s less stimulating small gape, and the parent warblers feed it generously. —L.H.
Elephants can die from herpes viruses
Two herpes viruses new to science can attack and kill elephants, pathologists report.
These are the first herpes viruses found in elephants, says codiscoverer Laura K. Richman of the Johns Hopkins Medical Institutions in Baltimore. The viruses hold special interest because they jump from one kind of elephant to another in zoos that are trying to protect the endangered species.
Many animals, from people to fish, suffer from cold sores and other miseries of herpes infections. The discovery of elephant herpes, described in a Feb. 19 Science paper, is a whodunit solved by Richman, Gary S. Hayward from Johns Hopkins, and Richard J. Montali from the National Zoo in Washington, D.C. They set out in 1995 to find the killer of Kumari, the first apolitical elephant born inside Washington’s Beltway.
The 16-month-old died after a mysterious illness that took away her appetite, left her listless, and made her tongue turn purple. Her autopsy showed massive internal hemorrhaging. Microscopic examination of tissue and DNA analysis revealed a previously unknown herpes virus. The researchers found the same virus in preserved tissues from seven other Asian elephants that had died mysteriously in North American zoos.
The same infection also turned up in African elephants in zoos. Yet this closely related species seemed to suffer nothing more serious than skin nodules and small vaginal lesions. A normally minor African virus could be turning lethal when it jumps to a different species, Richman warns. Identifying the infection early, in part by the purple tongue, allowed zookeepers in Missouri to save one young elephant with massive doses of the human herpes drug famciclovir.
The researchers have also discovered a related herpes virus that killed a young African elephant. So far, the researchers have not found a clue to its source. —S.M.
Because the common cuckoo can’t display a nestful of gaping reed warbler beaks (left), it begs by imitating a chorus of chicks.
When antlers grew too large
With antlers that can spread 2 meters, moose are the giants of the modern deer universe, but these big-nosed browsers pale in comparison with the extinct Irish elk. An ice age inhabitant of Europe and Asia, the Irish elk evolved antlers reaching
3 meters across and weighing 40 kilograms—too big for the animals’ own good, according to a new analysis of antler growth.
“People have always been interested in the Irish elk because they had the largest antlers of any deer. And they have always guessed what limited antler growth and why did they go extinct when the other deer didn’t,” says Ron A. Moen of the University of Minnesota-Duluth.
Moen and his colleagues used physiological information about moose to analyze antler growth in Irish elk. They calculate that males deposited more than 60 grams of calcium and 30 g of phosphorus daily into the growing antlers during midsummer. Diet would have provided most of these nutrients, but not all. The remainder would have been leached out of the animal’s skeleton during summer and replaced later, the researchers report in the February Evolutionary Ecology Research.
Some of the largest and last Irish elk lived in Ireland itself. They went extinct there during the final phase of the ice age, a 1,000-year-long cold snap called the Younger Dryas. At that time, glaciers covered much of the island, and tundra replaced forests.
According to the physiological model constructed by Moen and his coworkers, Irish elk ran into nutritional problems during the Younger Dryas. Their diet would have provided enough calcium and protein but not enough phosphorus and total calories. The males were able to grow big antlers during summer and thus could mate, but ones with the largest racks would have suffered later in the year when they could not restore their bone density or their fat reserves, says Moen.
Paleontologists have previously suggested that food limitations may have harmed Irish elk, but the new study is the first to quantify the nutritional requirements of the extinct species, says Adrian M. Lister, a paleontologist at University College London who studies Irish elk. —R.M.
Turtles and crocs: Strange relations
A new genetic study chops up the traditional reptile family tree by asserting that turtles are the closest living kin of crocodiles.
Generations of paleontologists have regarded turtles as outsiders among modern reptiles—holdovers from an ancient group called anapsids that lack holes in the sides of their skulls. Living reptiles and birds have two holes in the sides of their skulls and are termed diapsids. The new evidence, however, suggests that crocodiles are closer to turtles than they are to lizards, snakes, and birds—meaning that turtles sit smack in the middle of the reptile tree, rather than off to the side. S. Blair Hedges and Laura L. Poling of Pennsylvania State University in State College describe their work in the Feb. 12 Science.
These results confirm the findings from a previous molecular study that used fewer genes (SN: 12/5/98, p. 358). “It really solidifies the picture for the molecular data,” says paleontologist Olivier C. Rieppel of the Field Museum of Natural History in Chicago. His own studies of fossil reptiles have also challenged the conventional interpretation of turtle origins.
Paleontologists will find other aspects of the genetic results perhaps even more disturbing than the news regarding turtles. Hedges and Poling provide some of the first DNA analysis of tuataras, a group of four-legged reptiles that look superficially like lizards and are regarded as their closest living relatives. The analysis by Hedges and Poling, however, places tuataras nearer to crocodiles than to lizards. “From a paleontological point of view, I cannot even begin to imagine how tuatara could not be [closely] related to lizards and snakes,” says Rieppel. —R.M.
Ghostly magnetism comes from nowhere
Magnetism starts small. A substance becomes magnetic from the alignment of particles, such as some atoms or electrons that behave as tiny bar magnets. The discovery of a magnetic material with virtually no sign of such micromagnets, known as magnetic moments, has physicists stumped.
“There are just no moments other than a few free electron spins in there,” says Zachary Fisk of Florida State University in Tallahassee of a variant of calcium hexaboride that he and his colleagues are studying. “It doesn’t make sense” to see magnetic effects from so few elements. The researchers were probing the material’s electronic traits when they made the surprising discovery reported in the Feb. 4 Nature.
The finding revives a 60-year-old debate about the magnetic influence of low densities of electrons. Nobel laureate Eugene Wigner and others suggested how dilute clouds of so-called conduction electrons, which roam freely in a metal, might become ordered and generate magnetism. Other theorists countered that the spins of conduction electrons are usually randomly oriented, with every up spin canceled by a down spin.
Since the early 1980s, however, computer calculations have indicated that some types of magnetically effective ordering of scarse electrons can occur. Fisk and his colleagues may now have come up with experimental evidence.
The magnetism of the calcium-boron compound, which also includes a little lanthanum, is about a thousandth that of iron, Fisk estimates. Not only was that magnetism surprising, but its persistence up to 327°C has also stunned researchers.
Ordinarily, weak micromagnets fall out of alignment—canceling magnetism—at a much lower temperature than strong micromagnets. “Here that is absolutely not true,” says Hans R. Ott of the Federal Institute of Technology in Zurich. The new compound’s maximum magnetic temperature uncharacteristically approaches iron’s, 770°C.
No atoms in the compound have the requisite electronic configurations to generate magnetic moments, Ott says. “I can’t tell you how, but the moments somehow form in this very-low-density [conduction] electron ensemble.” —P.W.
Making magnetism flip twice, by design
Novel magnetic materials are out there, waiting to be discovered, but finding them is a hit-or-miss proposition. A Japanese team now reports it may have devised a straight path from theory to materials with specific, desirable traits.
When placed in a magnetic field, some materials develop magnetism with the same polarity, while others develop an opposing field. As described in the Feb. 8 ^ , the team created a new powder whose magnetic polarity flips twice as temperature climbs from absolute zero.
Such a double reversal was first reported in another material last year. This time, however, the researchers deliberately chose to make their new substance with the specific trait. “This is the first case of a new magnet predicted by theory,” says Kazuhito Hashimoto of the University of Tokyo and Kanagawa Academy of Science and Technology in Atsugi.
By incorporating an assortment of metal ions into a crystalline, chromium-based compound, the researchers cause polarity to flip at 35 kelvins and then flip back at 53 K. Between those temperatures, a negative magnetism takes over as one of the ion types, which aligns atomic spins contrary to an applied magnetic field, outweighs the positive responses of other ions.
The researchers expect their directed design to apply to a chemical family that includes the dye called Prussian blue. The double-flip material, a member of that family, is not likely to find practical use. However, Hashimoto and his colleagues are currently creating other magnetic materials, such as ones
that respond to light, with commercial promise. —P.W.