Abstract

The skin of congenic haired and hairless HRS/J mice has been established as a model in which to study determinants of dioxin induced toxicity. Both genotypes carry high affinity cytosol receptor and respond to dioxin exposure with the induction of epidermal aryl hydrocarbon hydroxylase activity. In addition, skin of the hairless (hr/hr), but not of the haired (hr/+ or +/+), mice responds to dioxin exposure with well defined pattern of morphologic changes. It has been proposed that in the hr/hr genotype, dioxin activates an additional battery of genes associated with proliferative/metaplastic skin changes, and that this activation is under genetic control (at the hr locus). This proposal outlines studies to pursue this hypothesis by further comparing the changes in cutaneous morphology and biochemical reactions in skin of congenic HRS/J mice in vivo and in vitro in response to dioxin exposure. Some of the specific biochemical reactions proposed for study are: epidermal ornithine decarboxylase, S-adenosyl methionine decarboxylase, and epidermal transglutaminase activity, cutaneous lipid biosynthesis, DNA synthesis, effect of anti-inflammatory agents on the above parameters, and localization of sites of disposition of dioxin in skin using autoradiographic studies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
1R01ES003597-01
Application #
3251022
Study Section
(SSS)
Project Start
1985-02-01
Project End
1988-01-31
Budget Start
1985-02-01
Budget End
1986-01-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Connor, M J; Sidell, N (1997) Retinoic acid synthesis in normal and Alzheimer diseased brain and human neural cells. Mol Chem Neuropathol 30:239-52
Ajie, H O; Connor, M J; Lee, W N et al. (1995) In vivo study of the biosynthesis of long-chain fatty acids using deuterated water. Am J Physiol 269:E247-52
Connor, M J; Puhvel, S M; Sakamoto, M et al. (1994) The hr locus and the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in newborn mice. Arch Toxicol 69:87-90
Connor, M J; Nanthur, J; Puhvel, S M (1994) Influence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on TNF-alpha levels in the skin of congenic haired and hairless mice. Toxicol Appl Pharmacol 129:12-5
Puhvel, S M; Connor, M J; Sakamoto, M (1991) Vitamin A deficiency and the induction of cutaneous toxicity in murine skin by TCDD. Toxicol Appl Pharmacol 107:106-16
Puhvel, S M; Sakamoto, M; Reisner, R M (1989) Effect of TCDD on the density of Langerhans cells in murine skin. Toxicol Appl Pharmacol 99:72-80