Nicotine spurs vessel growth, maybe cancer.

More than 4,000 chemicals make up cigarette smoke, and many of them can damage a person's health. But the bete noire of the lot is nicotine, a compound that is simultaneously pleasure-inducing, addictive, and--at high doses--poisonous. A new study adds another trait: Nicotine in mice has spawned the growth of new blood vessels and thus promoted cancer.

Blood vessel formation, or angiogenesis, can play a positive or negative role in health. Some researchers are inducing angiogenesis in heart-disease patients to help them rebuild damaged heart muscle (SN: 2/28/98, p. 132). Meanwhile, scientists fighting cancer are trying to thwart angiogenesis and thus the flow of oxygen and nourishment to tumors.

In the new study, the researchers had assumed that nicotine would impair angiogenesis. "We went into this study with the wrong hypothesis," says John P. Cooke, a cardiologist at Stanford University School of Medicine. To his surprise, laboratory cultures of human blood vessels grew well when exposed to nicotine in moderate doses. Nicotine also cut the rate of programmed cell death in those cultures.

Intrigued, Cooke and his colleagues began testing the effects of nicotine in mice. For one experiment, they implanted human-lung cancer tissues in the animals. They then gave some mice drinking water laced with nicotine in doses mirroring the amounts ingested by cigarette smokers.

The mice getting nicotine experienced more rapid tumor growth than did mice that were not given nicotine, the researchers report in the July NATURE MEDICINE.

In a group of mice without tumors, the researchers measured the effect of nicotine on atherosclerosis, the formation of fatty plaques in arteries. Mice receiving nicotine in their drinking water had larger plaques than mice getting plain water, the researchers report. Atherosclerotic plaques "grow like coral reefs; they are full of living cells," Cooke says. Nicotine induces vessel growth to feed these plaques, he says.

In other mice, the researchers stopped blood flow to one hind limb. Animals getting nicotine experienced double the growth of new blood vessels compared with mice not getting nicotine. Here, the angiogenesis benefited the mice.

"These are interesting conclusions that will need to be followed up," says Byron L. Olson, a biochemist at Indiana University School of Dentistry in Indianapolis. The nicotine-cancer link implied by angiogenesis could explain part of the association between mouth cancers and chewing tobacco, he says.

Researchers could look for drugs to block the action of nicotine in cases in which it's harmful, says Cooke. Conversely, nicotine's angiogenic qualities might have therapeutic value in people with injured tissues, he says.

The work indicates that excessive use of nicotine patches or gum may have a cost, Cooke adds, although it shouldn't dissuade people from short-term use of these products for smoking cessation.