Male Rats Given Drug Known to Cause Mutations : Birth Defects, Fathers’ Exposure to Chemicals Linked

Men who have been cured of cancer by drug therapy or who have had persistent exposure to certain toxic chemicals may run an increased risk of siring children with birth defects, according to a new study.

The study provides the first strong evidence that fathers can pass along the effects of chemical exposure to their children.

It has long been known that exposure of women to certain chemicals before or during pregnancy can produce birth defects in the children. Many scientists and laymen have suspected that the same phenomenon can occur with men.

Agent Orange Effects

Vietnam veterans, for example, have long argued that their exposure to the defoliant Agent Orange has led to birth defects in children born after their return to the United States. Men exposed to chemicals in their workplaces have made the same argument.

The only support for such arguments, however, has been epidemiological studies in which scientists identified a group of individuals with a particular type or class of birth defects and, working backward, tried to identify a common factor--such as exposure to a chemical--that might explain the abnormality. Such studies are notoriously susceptible to bias from ethnic and socioeconomic factors, according to Nigel Brown of the Medical Research Council in Carshalton, England.

The new study, reported in the most recent issue of the British journal Nature by Bernard Robaire and his colleagues at McGill University in Montreal, provides the first direct evidence of such a link.

Effects of Drug on Rats

Robaire, Jacquetta Trasler and Barbara Hales studied the effects in rats of the drug cyclophosphamide, which is used in treating Hodgkin’s disease and other cancers.

Cyclophosphamide is known to cause mutations in bacteria and birth defects when administered to pregnant females. Toxic anti-cancer drugs such as cyclophosphamide have also been shown to cause new cancers several years after a patient has been cured of the original malignancy.

“We were concerned about the effects cyclophosphamide might have on the reproductive systems of young men who had been cured of Hodgkin’s,” Robaire said in a telephone interview. “We expected to find that the drug impaired sperm production or had some other readily apparent effect (on laboratory rats).

“Instead, we found that the reproductive system remained superficially normal, but that the number of spontaneous abortions and birth defects of offspring from females mated with the rats increased significantly.”

Editorial Caution

In an editorial accompanying the Robaire report, Brown cautioned that the number of male rats studied is relatively small and that there are problems in extrapolating results obtained in laboratory animals to effects in man.

Nonetheless, Brown noted, “it would be extremely foolish to advise anything other than extreme caution over the exposure of humans to chemical mutagens when our understanding of the quantitative risk to future generations is so rudimentary.”

Robaire, meanwhile, is attempting to discover whether the effects of cyclophosphamide on the reproductive system are reversed when the animal is no longer exposed or whether they can be blocked with other drugs.