? ? Benzo(a)pyrene (BaP) is an ubiquitous environmental toxicant that belongs to the polycyclic aromatic hydrocarbon (PAH) family of compounds and causes toxicity and cancer to a variety of organs. Our preliminary studies have demonstrated that neonatal administration of rats with resveratrol (RVT) reduces BaP induction of the cytochrome P450 (CYP) family of enzymes in adult rats subsequent to exposure to BaP, with a concomitant reduction in the formation and distribution of reactive metabolites in plasma and target tissues. Our proposed studies will test the hypothesis that RVT modulates BaP-induced colon carcinogenesis through cytochrome P450 (CYP) mediated metabolic pathways. A related hypothesis that will be tested in our studies is that the bioavailable dose of BaP that contributes to toxicity/cancer during a lifespan can be altered by """"""""imprinting"""""""" with RVT treatment during the neonatal period, and that such an action, if ultimately translated into human studies, could have a significant effect on the quality and perhaps even the extent of life, in general, and in reducing the onset of colorectal cancer, in particular. More than 90 million Americans - 58 % of whom are men -- have or are at risk of developing cancer of colon and rectum, and the treatment costs are estimated to be $8.4 billion annually in the U.S. Since it is estimated that diet contributes to 80% of the known colorectal cancer cases, and because of PAH's ubiquity in foods and in environment due to industrial emissions, it is not unreasonable to attribute environmental exposure serving as one of the factors in initiating or accelerating colorectal cancer cases. We will test our hypotheses in adult male transgenic mice with the following specific aims: 1. Investigate the chemopreventive effect of neonatal resveratrol on BaP-DNA adduct formation, persistence and BaP-induced adenomas in colon and rectum of adult ApcMin mice; and 2. Determine whether neonatal exposure to resveratrol alters the expression and activities of BaP biotransformation enzymes and metabolite profile in adult ApcMin mice. This pilot project will provide important new information regarding the contribution of phytochemicals such as RVT towards delaying or preventing the development of colorectal carcinogenesis. Also, the data obtained will be useful for assessment and/or synthesis of other naturally occurring plant-based chemicals that could be tested in the early life as a means of preventing the development of cancer in adult life, thus improving the quality of life. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
1R03CA130112-01
Application #
7321591
Study Section
Special Emphasis Panel (ZCA1-SRRB-F (M1))
Program Officer
Ross, Sharon A
Project Start
2007-08-20
Project End
2009-07-31
Budget Start
2007-08-20
Budget End
2008-07-31
Support Year
1
Fiscal Year
2007
Total Cost
$73,250
Indirect Cost
Name
Meharry Medical College
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
041438185
City
Nashville
State
TN
Country
United States
Zip Code
37208
Rekhadevi, P V; Diggs, D L; Huderson, A C et al. (2014) Metabolism of the environmental toxicant benzo(a)pyrene by subcellular fractions of human ovary. Hum Exp Toxicol 33:196-202
Diggs, Deacqunita L; Myers, Jeremy N; Banks, Leah D et al. (2013) Influence of dietary fat type on benzo(a)pyrene [B(a)P] biotransformation in a B(a)P-induced mouse model of colon cancer. J Nutr Biochem 24:2051-63
Archibong, Anthony E; Ramesh, Aramandla; Inyang, Frank et al. (2012) Endocrine disruptive actions of inhaled benzo(a)pyrene on ovarian function and fetal survival in fisher F-344 adult rats. Reprod Toxicol 34:635-43
Diggs, Deacqunita L; Huderson, Ashley C; Harris, Kelly L et al. (2011) Polycyclic aromatic hydrocarbons and digestive tract cancers: a perspective. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 29:324-57
Huderson, Ashley C; Harris, Deacqunita L; Niaz, Mohammad S et al. (2010) Effect of benzo(a)pyrene exposure on fluoranthene metabolism by mouse adipose tissue microsomes. Toxicol Mech Methods 20:53-8
Harris, Deacqunita L; Washington, Mary K; Hood, Darryl B et al. (2009) Dietary fat-influenced development of colon neoplasia in Apc Min mice exposed to benzo(a)pyrene. Toxicol Pathol 37:938-46
Wang, Zefen; Yang, Hong; Ramesh, Aramandla et al. (2009) Overexpression of Cu/Zn-superoxide dismutase and/or catalase accelerates benzo(a)pyrene detoxification by upregulation of the aryl hydrocarbon receptor in mouse endothelial cells. Free Radic Biol Med 47:1221-9
McCallister, Monique M; Maguire, Mark; Ramesh, Aramandla et al. (2008) Prenatal exposure to benzo(a)pyrene impairs later-life cortical neuronal function. Neurotoxicology 29:846-54
Harris, Deacqunita L; Hood, Darry B; Ramesh, Aramandla (2008) Vehicle-dependent disposition kinetics of fluoranthene in Fisher-344 rats. Int J Environ Res Public Health 5:41-8
Archibong, Anthony E; Ramesh, Aramandla; Niaz, Mohammad S et al. (2008) Effects of benzo(a)pyrene on intra-testicular function in F-344 rats. Int J Environ Res Public Health 5:32-40

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