A nonhuman primate model, the patas monkey, is used to enhance our understanding and development of management strategies regarding human cancer risk related to chemical carcinogen exposure. The model has proved to be uniquely useful in three ways: firstly, to provide human-related data that could not be obtained with rodents because of extreme differences, for example, in perinatal carcinogenesis; secondly, to confirm phenomena established in rodents, before expensive, long-term human trials are undertaken; and thirdly, to reveal primate-unique in vivo phenomena that would never be discovered with rodents or with in vitro studies. We make the model widely available to intramural and extramural collaborators, and at the present time are participating in studies of in vivo metabolism of the tobacco- specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and its modulation by the chemopreventive agent, phenethylisothiocyanate; metabolism of environmental nitrosamines by esophagus; in vivo metabolism of food-contaminant levels of the arylamine carcinogen 2-amino-1- methyl-6-phenylimidazo[4,5-b]pyridine (PhIP); and DNA adducts in placenta of the chemotherapeutic agent, cisplatin. We have acquired striking data relevant to a potential contribution of environmental nitrosamines to risk of gastrointestinal and urinogenital tract cancer, and of perinatal carcinogenesis, showing that tissues thought, on the basis of rodent studies, to be insensitive to these nitrosamines are, in monkeys, quite sensitive to causation of promutagenic DNA damage. Further, ethanol, a major risk factor for certain human cancers, greatly enhanced (5- to 18-fold) the level of DNA damage in many of these tissues. Of particular public health relevance are new studies to examine potential genotoxic effects in monkey fetal tissues of azidothymidine (AZT), an anti-HIV drug being given in increasing frequency to infected pregnant women and their newborns. While this compound is of great benefit in preventing HIV transfer to fetuses, it is a selective carcinogen in adult mice but has not been tested perinatally.
