Critical windows of exposure for children's health: Cancer in human epidemiological studies and neoplasms in experimental animal models

In humans, cancer may be caused by genetics and environmental exposures; ho wever, in the majority of instances the identification of the critical time window of exposure is problematic. The evidence for exposures occurring du ring the preconceptional period that have an association with childhood or adulthood cancers is equivocal. Agents definitely related to cancer in chil dren, and adulthood if exposure occurs in utero, include: maternal exposure to ionizing radiation during pregnancy and childhood leukemia and certain other cancers, and maternal use of diethylstilbestrol during pregnancy and clear-cell adenocarcinoma of the vagina of their daughters. The list of env ironmental exposures that occur during the perinatal/postnatal period with potential to increase the risk of cancer is lengthening, but evidence avail able to date is inconsistent and inconclusive. In animal models, preconcept ional carcinogenesis has been demonstrated for a variety of types of radiat ion and chemicals, with demonstrated sensitivity for all stages from fetal gonocytes to postmeiotic germ cells. Transplacental and neonatal carcinogen esis show marked ontogenetic stage specificity in some cases. Mechanistic f actors include the number of cells at risk, the rate of cell division, the development of differentiated characteristics including the ability to acti vate and detoxify carcinogens, the presence of stem cells, and possibly oth ers. Usefulness for human risk estimation would be strengthened by the stud y of these factors in more than one species, and by a focus on specific hum an risk issues.