The widely used painkiller acetaminophen -- sold as a nonprescription drug under such brand names as Tylenol, Datril and Panadol -- is being studied by two government agencies as a possible cancer-causing agent.

Both the National Cancer Institute, part of the National Institutes of Health, and the National Toxicology Program, a research arm of the National Institute of Environmental Health in North Carolina, are investigating whether this popular analgesic may cause cancer either through long-term use or by taking high doses.

In addition to these new studies under way, several other factors are part of the scientific debate on whether there is a link between acetaminophen and cancer. Among them are:

*The chemical similarity between phenacetin, now banned in the United States because of its association with kidney cancer, and acetaminophen. The body metabolizes phenacetin by breaking it down in the liver to acetaminophen, and another compound called p-phinitidin.

*A 1983 NCI study showing that people who took both acetaminophen and phenacetin for three years or more had four times the expected rate of a type of cancer that affects a part of the kidney known as the pelvis. Because it was impossible for researchers to separate the individual effects of these drugs, the new NCI study is now under way to look at the effects of acetaminophen alone.

*A 1983 animal study by British researchers Antonia and Bojan Flaks that found that administering 10 times the daily human dose of acetaminophen caused malignant liver tumors in more than 80 percent of mice studied during an 18-month period. A similar study in rats, also by the Flakses, found that acetaminophen produced benign kidney tumors in these animals.

Any one of these studies "might not have been that worrisome," says Dr. Robert Hoover, chief of NCI's environmental epidemiology branch. Taken together, however, they provide reason for continued study, he says.

Many questions about acetaminophen -- and the studies of this drug -- need to be answered, researchers say, since conflicting information appears in the scientific literature. Most recently, two Japanese groups attempted to repeat the Flaks study and reported earlier this year -- in the Japanese Journal of Hygiene and the Japanese Journal of Cancer Research -- that giving acetaminophen to mice and rats had no cancer-causing effects.

Other controversy about acetaminophen centers on criticism of the Flaks study. At issue is the fact that more than half the mice receiving high doses (about 10 times the human dose) died in the first 48 hours of the 18-month study, which critics say invalidates the data because the doses were so toxic to the animals.

Bojan Flaks, however, notes, "We repeated the study subsequently and got no deaths at all" when the drug was administered but found similar tumor-causing effects.

"The Flaks study was really a very seriously flawed study," says Dr. Thomas Gates, medical director of McNeil Consumer Products, the company that produces Tylenol -- the largest-selling acetaminophen-containing painkiller in the United States.

Spokesmen for Johnson & Johnson, parent company of McNeil, also note that although the known cancer-causing agent phenacetin breaks down in the body into acetaminophen and p-phinitidin, one of the Japanese studies suggests that it is p-phinitidin that causes cancer -- not acetaminophen.

"These two Japanese studies are extremely well done . . . clean as a whistle, and should certainly override any findings in the Flaks study," Gates says.

But based on his findings, Flaks says that acetaminophen "looks as though it is tumorogenic [produces tumors] . . . I think that it is a weak carcinogen [cancer-causing agent]."

One study that is expected to help resolve the issue is being done by the National Toxicology Program. NTP investigators routinely screen widely used drugs that were introduced to the market before the Food and Drug Administration began requiring drug manufacturers to show proof of safety and effectiveness. The NTP study on acetaminophen, begun in 1978 -- well before the results of the Flaks study were known -- is looking at whether this painkiller causes cancer in mice and rats. Results will be released sometime next year, says NTP chemist Richard Irwin, who heads the study.

Acetaminophen (pronounced a-seat-a-MIN-a-fin), was introduced to the American public some 90 years ago. It acts on the part of the brain known as the hypothalamus to increase loss of body heat and to lower fever. Like aspirin, acetaminophen can also control pain. Overdoses of acetaminophen, however, can be far deadlier than aspirin by causing severe and often irreparable liver damage and death.

But at normal dosages, acetaminophen also has two major advantages over aspirin: It doesn't cause stomach irritation, and it's not associated with the development of Reye's syndrome, the deadly disease linked to use of aspirin in children suffering from influenza and chicken pox.

The American Academy of Pediatrics Committee on Infectious Diseases noted in 1981 that there were "sufficient reports showing an association with aspirin use particularly in children with fever or acute febrile illnesses, particularly from influenza or chicken pox and the subsequent development of Reye's syndrome" to recommend using "an aspirin substitute such as acetaminophen for controlling fever in children with influenza or chicken pox."

But this new controversy about acetaminophen probably does not mean that parents should worry about giving aspirin-free painkillers to control fever in their children.

"There is absolutely no basis for concern here," says McNeil's Gates.

"I'm not terribly worried," adds Dr. Robert Temple, director of the Food and Drug Administration's office of drug research and review. "The Flaks study has been known to us for a while. It certainly is of some interest.

"But the fact that there are reassuring Japanese studies helps. I don't think that we've really discovered anything important yet . . . It's highly premature to abandon a good and well tolerated drug."

And NCI's Hoover notes that "I'm not going to alter my own practice of treating my kids with Tylenol [when they have a fever]."

But several scientists agree that these new findings may have some important implications for people who must take acetaminophen for long periods of time.

"The concerns in the past about phenacetin and currently about acetaminophen would really only refer to abuse and long term use of these drugs," says Hoover.

"What we don't know," says Bojan Flaks, "is how many people are there taking their doses of acetaminophen day after day after day and either holding the maximum level or even exceeding a little bit.

"Among that population may be a small number who suffer from chronic liver damage as a result of this. The question that raises in my mind: Could those people be at risk for cancer?"