1. Sponsor Organization: USDA-CSREES

2. Project Title: Keratinocyte Culture Model: Toxic Mechanisms

3. Project Focus:

• Project Primary Focus: Human Health Effects
• Project Secondary Focus:

4. Description:

OBJECTIVES: Demonstrate that cultured epidermal cells are a valuable resource for elucidating mechanisms of toxicity. Specifically, the cytochrome P450 isozymes responsible for activation of polycyclic aromatic hydrocarbons, heterocyclic amines and organophosphate pesticides will be determined. Initial work with rat cells will be extended to those from farm animals. APPROACH: First, individual P450 isozymes will be expressed in a rat cell line in which the endogenous genes are silent. These cells will then be treated with a polycyclic hydrocarbon (3- methylcholanthrene), a heterocyclic amine (Trp-P-1 or Trp-P-2), or an organophosphate (chlorpyrifos or diazinon). The resulting toxicity, metabolites and, where appropriate, mutagencity will be examined. P450 expression in epidermal and esophageal cells from farm animals will be characterized and the response of these cells to polycyclic aromatics, heterocyclic amines and organophosphates will be assessed.

5. References:

1. Author: Rea MA, Phillips MA, Degraffenried LA, Qin Q, Rice RH
   Title: Modulation of human epidermal cell response to 2,3,7,8-tetrachlorodibenzo-p-dioxin by epidermal growth factor.
   Citation:
   Year:
   

2. Author: Kachinskas DJ, Qin Q, Phillips MA, Rice RH
   Title: Arsenate suppression of human keratinocyte programming.
   Citation: Mutation Res
   Year: 1997
   

6. Inventory Category:

• Primary: Measure
• Secondary:

7. Inventory Subcategory:

• Primary: Basic Research
• Secondary:

8. Keywords for Experimental System/Species:

• Species:
  • Mammal
• Study Type:
  • In Vitro
  • Laboratory Study
• Fate and Transport:

9. Keywords for Experimental Endpoints:

• Health Effect:
  • Carcinogenesis
• Hormonal Measures:
• Level Of Study:
  • Biochemistry
  • Gene Expression
• Chemistry Metabolism:
  • Cytochrome P450
• Life Stage:
• Risk Assessment:

10. Chemical Agents:

• Dioxins
• Pahs
• Pcbs

11. Performing Institution:

• Environmental Toxicology ;University of California ;Davis, CA 95616 ;

12. Contact:

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