March 15, 1997

Does yo-yo dieting pose cancer threat?

by J. Raloff

Several studies have linked obesity to a heightened risk of breast cancer. Though the mechanism has remained elusive, some scientists have suggested that excess body fat may spur this and other hormone-sensitive tumors because fat produces its own estrogen.

A provocative new animal study now finds that this old theory may be right -- but for a different reason.

Robert M. Bigsby of the Indiana University School of Medicine in Indianapolis and his colleagues have focused on estrogen and two estrogen-mimicking compounds that the body stores in fat: beta-hexachlorocyclohexane (™-HCH) and DDT. ™-HCH, a variant of the active ingredient in the pesticide lindane, occurs in commercial preparations. Widespread use has made DDT and ™-HCH ubiquitous in nature, including the fat of most people.

In experiments described in the March 1 Cancer Research, scientists removed the ovaries from female mice and injected the animals on three successive days with estrogen, ™-HCH, or DDT. Without ovaries, the mice could not make their own estrogen. All three chemicals stimulated temporary growth of the uterus, which soon returned to normal size.

Two weeks later, the researchers put such mice on a 3-day fast, which triggered a burning of stored body fat. During the fast, DDT stayed in the fat, but animals treated with ™-HCH released the compound into their bodies. This release again spurred dramatic uterine growth -- a hallmark of estrogen's presence. Had seeds of a tumor been present, this pollutant probably would have spurred their growth too, observes Bigsby.

After the fast, the uteruses of mice that had been treated with ™-HCH were "nearly as large as immediately after the 3-day chemical treatment," Bigsby notes.

Though he acknowledges that the doses he administered seem large, he also notes that the concentrations which probably developed in fat "should be comparable" to those reported in a 1990 study of Finnish women.

Earlier, the Indiana-based team had shown that ™-HCH spurs the growth of breast cancer cells, but in an unusual way. "It didn't do the normal thing that estrogens and DDT do," notes physiologist Rosemary Steinmetz, who led that study.

Not only did ™-HCH not bind to the estrogen receptor -- at least, not at the usual site -- it also didn't turn on the normal switches for estrogen-responsive genes. Steinmetz's follow-up studies with bisphenol-A, another environmental estrogen (SN: 4/6/96, p. 214), suggest that it, too, works without binding to that receptor.

The two Indiana reports "provide empirical confirmation of a theory that we've been developing," says toxicologist Devra Lee Davis of the World Resources Institute in Washington, D.C., referring to three papers that she and Michael Osborne of the Strang Cancer Prevention Center in New York are about to publish. They argue that not all estrogen mimics work through the estrogen receptor to increase cancer risk. Some may instead alter DNA to produce effects similar to those of estrogen.

The Indiana data also could be important for people who repeatedly lose and gain weight, contends endocrinologist H. Leon Bradlow of the Strang Center: Every time such yo-yo dieters drop in weight, they risk releasing substances stored in fat, thus exposing their organs to toxic chemicals.

Helena Mussalo-Rauhamaa of Helsinki University Hospital agrees, saying epidemiologists should begin surveying for yo-yo dieting when they probe cancer links to pollutants. In 1990, she found that breast cancer patients had more ™-HCH in their fat than women without cancer. Clearly, she argues, ™-HCH does not appear as benign as most chemistry handbooks allege.

Indeed, contends Davis, the fact that lindane is still used on children to kill head lice "is appalling."

References:

Bigsby, R.M., A. Caperell-Grant, and B.V. Madhukar. 1997. Xenobiotics released from fat during fasting produce estrogenic effects in ovariectomized mice. Cancer Research 57(March 1):865.

Steinmetz, R., A. Caperell-Grant . . .R.M. Bigsby. 1996. Novel estrogenic action of the pesticide residue beta-hexachlorocyclo hexane in human breast cancer cells. Cancer Research 56(Dec. 1):5403.

Allen, R.H., et al. In press. Breast cancer and pesticides in Hawaii. Environmental Health Perspectives.

Bradlow, H.L., et al. 1995. Effects of pesticides on the ratio of 16 alpha/2-hydroxyestrone: A biologic marker of breast cancer risk. Environmental Health Perspectives 103, Supplement 7(October):147.

Davis, D.L. . . .M.P. Osborne. In press. Environmental influences on breast cancer risk. Science and Medicine.

Davis, D.L. In press. Hormones, hormone metabolism, environment and breast cancer. Environmental Health Perspectives.

Davis, D.L. . . .M.P. Osborne, and H.L. Bradlow. In press. Medical hypothesis: Bifunctional genetic-hormonal pathways to breast cancer. Environmental Health Perspectives.

Davis, D.L., and H.L. Bradlow. 1995. Can environmental estrogens cause breast cancer? Scientific American 273(October):166.

Mussalo-Rauhamaa, H., et al. 1990. Occurrence of beta-hexachlorocyclohexane in breast cancer patients. Cancer 66(Nov. 15):2124.

Raloff, J. 1996. Estrogenic agents leak from dental sealant. Science News 149(April 6):214.

______. 1996. The pesticide shuffle. Science News 149(March 16):174.

______. 1995. Beyond estrogens. Science News 148(July 15):44.

______. 1995. Additional source of dietary 'estrogens'. Science News 147(June 3):341.

______. 1994. That feminine touch. Science News 145(Jan. 22):56.

______. 1994. The gender benders. Science News 145(Jan. 8):24.

______. 1993. EcoCancers. Science News 144(July 3):10.

Robert M. Bigsby
Obstetrics/Gynecology Research Laboratories
1001 Walnut Street (MF 102)
Indiana University School of Medicine
Indianapolis, IN 46202-5196
E-mail: rbigsby@indyvax.iupui.edu

H. Leon Bradlow
Strang Cancer Research Center
Box 231
Rockefeller University
1230 York Avenue
New York, NY 10021

Devra Lee Davis
Program on Health, Environment & Development
World Resources Institute
1709 New York Avenue, N.W.
7th Floor
Washington, DC 20006

Helena Mussalo-Rauhamaa
Department of Dermatology and Allergic Diseases
Helsinki University Central Hospital
Meilantie
00250 Helsinki
Finland

Rosemary Steinmetz
Obstetrics/Gynecology Research Laboratories
1001 Walnut Street (MF 102)
Indiana University School of Medicine
Indianapolis, IN 46202-5196

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