Studies on the structure and expression of human cytochrome p-450c

Conference · Fri May 01 04:00:00 EDT 1987 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6366135

Hines, R; Iversen, P; Bresnick, E; Heiger, W

The expression of cytochrome P-450c (P450c) is transcriptionally elevated upon exposure to many polycyclic aromatic hydrocarbons (PAH). This isozyme functions in the metabolic activation of these same compounds to their ultimate carcinogenic/toxic form. A clone for P-450c was isolated from a human lymphocyte library and has been used for studies on the structure of the human gene, both in comparison to other species and for comparisons within the human population. The overall structure of the P-450c gene has been highly conserved between rat and human, coding information being 90% identical. Southern blot analyses of random human DNA samples has demonstrated an aberrant hybridization pattern in about 11% of the samples studied. This pattern represents a second rare allele with a frequency of 0.01, or more likely, a duplication of the 5' half of the gene. Experiments have also been designed to examine sequences involved in the regulation of expression of P-450c by fusion of sequences from -1142 to +2434 to chloramphenicol acetyl transferase (CAT) as a reporter gene. Transfection of this construction into the human hepatoma cell line, HepG2, resulted in PAH responsive expression of CAT in transient expression assays.

• Research Organization: Univ. of Nebraska Medical Center, Omaha
• OSTI ID: 6366135
• Report Number(s): CONF-870644-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 46:6
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BIOLOGICAL EFFECTS
DISEASES
DNA
DNA SEQUENCING
GENES
HEPATOMAS
HYBRIDIZATION
HYDROCARBONS
MAMMALS
MAN
METABOLIC ACTIVATION
MOLECULAR STRUCTURE
NEOPLASMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
POLYCYCLIC AROMATIC HYDROCARBONS
PRIMATES
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES