The hypothesis to be tested is that exposure of mollusks to carcinogens in the environment, such as polycyclic aromatic hydrocarbons (PH), combined with tumor promoters (PCBs) causes p53 gene mutations and leads to leukemia. This hypothesis will be addressed as follows: 1) The applicant will extend analyses of p53 gene expression by comparing mollusks from sites with high and low contaminant levels. She will use reverse transcriptase/polymerase chain reaction-single strand conformation polymorphism (RT/PCR-SSCP) to evaluate p53 sequences and will address the hypothesis that p53 mutations occur in animals collected from PAH/PCB contaminated sites. 2) Normal clams will be exposed to PAH/PCB in a controlled laboratory environment to determine if mutant p53 is expressed and leukemia induced. Following in vitro fertilization, molluskan embryos will be exposed to PAH/PCB. The following determinations will be made: 1) The rate of embryogenesis following in vitro fertilization from the first polar body to metamorphosis (1.5 weeks post fertilization). 2) The pattern of wild type versus mutant p53 gene expression at precise stages during early embryonic development. 3) The induction of leukemia in young adults exposed during embryogenesis to PAH/Aroclor 1254.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA044307-10
Application #
2894699
Study Section
Special Emphasis Panel (ZRG2-MEP (03))
Program Officer
Liu, Yung-Pin
Project Start
1987-08-10
Project End
2001-03-31
Budget Start
1999-04-01
Budget End
2001-03-31
Support Year
10
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Marine Biological Laboratory
Department
Type
DUNS #
001933779
City
Woods Hole
State
MA
Country
United States
Zip Code
02543
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Jessen-Eller, K; Steele, M; Reinisch, C et al. (1998) Blockade of ryanodine receptors stimulates neurite outgrowth in embryos of Spisula solidissima. Biol Bull 195:206-7
Barker, C M; Calvert, R J; Walker, C W et al. (1997) Detection of mutant p53 in clam leukemia cells. Exp Cell Res 232:240-5
Harper, D M; Flessas, D A; Reinisch, C L (1994) Specific reactivity of leukemia cells to polyclonal anti-PCB antibodies. J Invertebr Pathol 64:234-7
Smolowitz, R M; Reinisch, C L (1993) A novel adhesion protein expressed by ciliated epithelium, hemocytes, and leukemia cells in soft-shell clams. Dev Comp Immunol 17:475-81
White, M K; Miosky, D; Flessas, D A et al. (1993) The expression of an adhesion-related protein by clam hemocytes. J Invertebr Pathol 61:253-9

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