Maturation or genesis of biochemical insult can be influenced by genetic, physiological and environmental factors. The perinatal period of development in humans and in rodents is recognized as a time during which critical organizational events or imprinting effects are still taking place in the central nervous system. Developmental regulators, such as hormones irreversibly direct maturational differentiation to take place in the brain to organize nerve endings that will direct the ontogeny and regulation of endocrine secretion. the critical period of brain growth in humans is primarily during the third trimester of pregnancy, while in laboratory rats the critical period is primarily during the last few days of pregnancy and the first week after birth. The fetus and newborn are consequently susceptible to numerous factors that can have deleterious effects on the developing organism. Neonatal exposure of rats to hormones or hormonally-active xenobiotics alters endocrine secretion, sexual behavior, hepatic metabolism and susceptibility for genotoxicity and carcinogenesis in adult animals. It is the object of this proposal to investigate the underlying mechanisms of altered activation/detoxication metabolism and genotoxicity in adult rats following neonatal exposure to diethylstilbestrol. We propose to 1) study the in vitro and in vivo metabolism of aflatoxin, 2) receiving pituitary transplants or growth hormone and 3) chemically lesioned in the hypothalamus during the neonatal period. High pressure liquid chromatography (HPLC) and spectrophotometry will be used for measuring metabolic end products and aflatoxin-DNA adducts. These experiments will provide us with kinetics of carcinogen-DNA adducts that lead to promutagenesis. We will gain information of the metabolism involved in activation/detoxication of a model procarcinogen. Investigations on the role of the hypothalamic-pituitary-gonadal axis on the expression of genotoxicity will extend the knowledge of imprinting effects for biochemical insult (carcinogenesis).
| Lamartiniere, C A; Moore, J; Holland, M et al. (1995) Neonatal genistein chemoprevents mammary cancer. Proc Soc Exp Biol Med 208:120-3 |
| Lamartiniere, C A (1990) Neonatal diethylstilbestrol treatment alters aflatoxin B1-DNA adduct concentrations in adult rats. J Biochem Toxicol 5:41-6 |
| Moore, S M; Lamartiniere, C A (1990) Diethylstilbestrol potentiates and testosterone antagonizes the action of 3-methylcholanthrene on benzo(a)pyrene metabolism in Hep G2 cells. J Biochem Toxicol 5:237-43 |
| Lamartiniere, C A; Pardo, G A (1988) Altered activation/detoxication enzymology following neonatal diethylstilbestrol treatment. J Biochem Toxicol 3:87-103 |
