Perinatal exposures may lead to increased risk of childhood cancers, as well as those later in life. Preconceptional parental, transplacental, and/or neonatal exposures may be involved. Studies with animal models are utilized to increase understanding of underlying cellular and molecular mechanisms. Transmammary neonatal exposures have received relatively little attention. We have studied exposure by this route to the carcinogenic nitrosamine, N-nitrosodimethylamine, which is present in tobacco smoke and other environmental sources. After administration to lactating rat mothers, N-nitrosodimethylamine caused formation in tissues of suckling infants of a DNA adduct known to be associated with tumor initiation. Furthermore, if the mother received ethanol at the same time, there was a 10-fold increase in these adducts in some tissues. These results indicate that transmammary exposures should receive further study. Another understudied exposure issue is that of transgenerational carcinogenesis. We are examining the effects of paternal exposure to chromium(III), a chemical widely encountered occupationally. Exposure of male mice to this chemical before mating leads to increased incidence of several types of neoplasms in the offspring. Preliminary results indicate that this is associated with changes in serum hormones in the offspring, and altered expression of a number of hepatic genes as studied by microarray, including insulin-like growth factor binding protein 1. AIDS Title:

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC005352-18
Application #
6433018
Study Section
(LCC)
Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Schmidt, Adele L; Anderson, Lucy M (2006) Repetitive DNA elements as mediators of genomic change in response to environmental cues. Biol Rev Camb Philos Soc 81:531-43
Anderson, Lucy M; Riffle, Lisa; Wilson, Ralph et al. (2006) Preconceptional fasting of fathers alters serum glucose in offspring of mice. Nutrition 22:327-31
Anderson, Lucy M (2006) Environmental genotoxicants/carcinogens and childhood cancer: bridgeable gaps in scientific knowledge. Mutat Res 608:136-56
Shiao, Yih-Horng; Crawford, Erik B; Anderson, Lucy M et al. (2005) Allele-specific germ cell epimutation in the spacer promoter of the 45S ribosomal RNA gene after Cr(III) exposure. Toxicol Appl Pharmacol 205:290-6
Anderson, Lucy M (2004) Introduction and overview. Perinatal carcinogenesis: growing a node for epidemiology, risk management, and animal studies. Toxicol Appl Pharmacol 199:85-90
Souliotis, Vassilis L; Sfikakis, Petros P; Anderson, Lucy M et al. (2004) Intra- and intercellular variations in the repair efficiency of O6-methylguanine, and their contribution to kinetic complexity. Mutat Res 568:155-70
Cheng, R Y S; Birely, L A; Lum, N L et al. (2004) Expressions of hepatic genes, especially IGF-binding protein-1, correlating with serum corticosterone in microarray analysis. J Mol Endocrinol 32:257-78
Anderson, Lucy M (2004) Predictive values of traditional animal bioassay studies for human perinatal carcinogenesis risk determination. Toxicol Appl Pharmacol 199:162-74
Cheng, Robert Y-S; Hockman, Tyler; Crawford, Erik et al. (2004) Epigenetic and gene expression changes related to transgenerational carcinogenesis. Mol Carcinog 40:1-11
Cisneros, Francisco Javier; Wilson, Ralph; Travlos, Gregory et al. (2003) Susceptibility to postnatal growth retardation induced by 5-AZA-2'-deoxycytidine in utero: gender specificity and correlation with reduced insulin-like growth factor 1. Life Sci 72:2887-94

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