By David N. Leff

On every can and bottle of booze, the surgeon general warns pregnant women not to drink alcoholic beverages (to avoid fetal alcohol syndrome). Now new research implicitly cautions expectant mothers not to OD on certain fruits, vegetables and dietary supplements. Does this imply the hazard of fetal broccoli syndrome?

Today's Proceedings of the National Academy of Sciences (PNAS), dated April 25, 2000, tells the story in an article titled: "Dietary bioflavonoids induce cleavage in the MLL gene and contribute to infant leukemia." Its senior author is hematologist Janet Rowley, a pioneer leukemia scientist at the University of Chicago. The co-lead authors are biochemists Pamela Strissel and Reiner Strick.

"MLL is a common leukemia gene, standing for 'myeloid lymphoid leukemia,' and residing on the long arm of human chromosome 11," Strissel told BioWorld Today. "There's a hypothesis that MLL has to do with transcription of genes, or in maintaining genes that are involved in hematopoietic development in their expressed state. Everybody's working on this now, to try to find out the function of its protein. MLL," she added, "is implicated in the acute leukemias, mainly in adults and children, and around 80 percent of infant leukemias.

"Infant leukemias are rare," Strissel pointed out, "with only 37 cases per million population in the U.S. But in some large Asian cities, a study in 1988 found that the incidence is twofold higher. That's largely due to the very high consumption in that part of the world of soybean-based foods - such as tofu, plus green teas and herbal medicines. It's pretty well accepted now," she added, "that infant leukemia occurs in utero."

The hypothesis espoused by the co-authors of today's PNAS paper, as well as by many other researchers, is that a family of natural food substances, the bioflavonoids, help perpetrate infant leukemia. Besides soybeans, many fruits and root vegetables - especially grapefruit, oranges, apples, berries, onions broccoli - are rich in bioflavonoids.

Diet Pill Works Like Anticancer Drug

"Bioflavonoids are not produced in the human body," Strick observed. "But beyond the produce of orchards and farms, they are available in much greater concentration in dietary supplement pills sold at health food stores."

"They actually work in the same way as some cancer chemotherapy agents, such as doxorubicin and VePesid (VP16)," said Strissel. "But these flavonoids come from plants and are modified by drug companies for chemotherapy. Nobody eats them."

However, millions of Americans do eat them in the form of dietary supplements. "We tested one called quercetin," Strissel recounted, "and it's a very large amount - 500 milligrams - that you can take per day, as recommended on the label. But the bottle doesn't say what it's recommended for. So if you consume these bioflavonoids when you're pregnant, either via diet at a very high amount or by taking quercetin pills, they could act like the cancer chemotherapy treatment.

"I don't think that's necessarily such a good idea," she went on, "especially for pregnant women who are carrying a developing fetus, which might be more sensitive to higher levels of these substances in particular."

Strick echoed this gestational caution: "It's common knowledge that what the mother eats will be going to her fetus. So all the bioflavonoids, as good as they are, can also go and harm the infant. Our concluding hypothesis now is: If the mother reaches a blood level of bioflavonoids ingested by foods and dietary supplements that goes over 5 to 10 microMolars, we think this could be harmful for the infant, because in the first weeks of gestation it is producing the first hematopoietic - blood-building - embryonic stem cells. And if there is now an inhibitor for topoisomerase II - one of the main proteins in the cell-division cycle - which actually could induce the cleavage in the MLL gene, we hypothesize that this opened and cleaved gene could recombine with other genes that we also find in adult leukemias, if these cells are perceived to grow as tumor cells.

"And another thing, not yet 100 percent known," Strick continued, "we hypothesize that if you eat a lot of bioflavonoids, especially in dietary supplements, it is possible that as a normal adult you will reach such a high bioflavonoid concentration in your blood that the leukemic transformation could also happen to you, not only to the infant."

The co-authors reported that half of the 20 bioflavonoids they tested caused DNA breaks in one small region of the MLL gene, and presumably on chromosome 11. This DNA damage was identical to that caused by the potent anticancer drugs, doxorubicin and VePesid. Most adult leukemias affect a different region of that MLL gene, but the breakpoints found in infant leukemias - as well as secondary leukemias - occur mainly in that small site altered by the bioflavonoids.

Secondary leukemias are a poetically unjust side effect of cancer chemotherapy. "We actually have some hints or evidence from the clinics," Strick pointed out. "Among patients treated only with chemotherapy, not flavonoids for another primary tumor - say breast or colon cancer and so on - all of a sudden 5 percent to 15 percent of these patients produce a so-called therapy-related secondary leukemia, which was not a primary tumor.

Easy On Flavonoid-Laced Supplement Pill

Strick has no message for cancer clinicians, but voiced "one kind of common-sense health lesson: Eat the normal fruits and vegetables you always ate, but don't overdo it with dietary supplements, especially during pregnancy. Because as we all see now, too much vitamin C, too much vitamin A, too much vitamin E is also not good for you. They produce a lot of other clinical diseases, and we want to just make the public somehow conscious of the fact that - besides bioflavonoid's undoubted benefits of maintaining blood vessels and scavenging free radicals - too much of that good thing can also be bad for you - and your unborn infant."

The co-authors also are planning an epidemiological study in which surveyors would ask the mothers of leukemic infants whether they had ingested undue amounts of fruits and vegetables and diet supplement pills during their pregnancy.