| Critical Windows of Exposure for Children's Health: Cancer in Human Epidemiological Studies and Neoplasms in Experimental Animal Models Lucy M. Anderson,1 Bhalchandra A. Diwan,2 Nicola T. Fear,3 and Eve Roman3 1Laboratory of Comparative Carcinogenesis; 2IRSP, SAIC Frederick, National Cancer Institute, FCRDC, Frederick, Maryland, USA; 3Leukaemia Research Fund, Centre for Clinical Epidemiology, University of Leeds, Leeds, United Kingdom Abstract In humans, cancer may be caused by genetics and environmental exposures ; however, in the majority of instances the identification of the critical time window of exposure is problematic. The evidence for exposures occurring during the preconceptional period that have an association with childhood or adulthood cancers is equivocal. Agents definitely related to cancer in children, 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 environmental exposures that occur during the perinatal/postnatal period with potential to increase the risk of cancer is lengthening, but evidence available to date is inconsistent and inconclusive. In animal models, preconceptional carcinogenesis has been demonstrated for a variety of types of radiation and chemicals, with demonstrated sensitivity for all stages from fetal gonocytes to postmeiotic germ cells. Transplacental and neonatal carcinogenesis show marked ontogenetic stage specificity in some cases. Mechanistic factors include the number of cells at risk, the rate of cell division, the development of differentiated characteristics including the ability to activate and detoxify carcinogens, the presence of stem cells, and possibly others. Usefulness for human risk estimation would be strengthened by the study of these factors in more than one species, and by a focus on specific human risk issues. Key words: cancer, chemical carcinogens, childhood, exposure, fetus, in utero, ionizing radiation, neonatal, postnatal, preconception. -- Environ Health Perspect 108(suppl 3) :573-594 (2000) . http://ehpnet1.niehs.nih.gov/docs/2000/suppl-3/573-594anderson/abstract.html The full version of this article is available for free in HTML format. |