The partial characterization of tumor necrosis factor-[alpha] resistance, and differential interferon-[alpha] and -[gamma] regulation of the indoleamine 2,3-dioxygenase gene in a human cell line

Thesis/Dissertation · Fri Jan 01 04:00:00 EST 1993

OSTI ID:7035382

Kimbro, K S

In order to understand the mechanisms of action of Tumor Necrosis Factor(TNF) on human tumor cells, the author has analyzed a TNF-resistant (TNFr) cell variant of ME180. Studies of the resistant clone showed an increase in in vitro generated free radical resistance, superoxide dismutase, and catalase mRNAs. The analysis of a TNFr clone and its karyotype compared to the parental line, suggest that TNFr could be due to an increase in free radical scavenger proteins and/or chromosomal aberrations. The second component of the thesis involves the analysis of another cytotoxic cytokine, interferon-[gamma], and its ability to induce indoleamine 2,3-dioxygenase (IDO). IDO is the rate limiting enzyme in the catabolism of tryptophan in most cell types. It is predominantly induced following treatment with IFN-[gamma], at a low level or not at all by IFN-[alpha] or-[beta]. The author has determined that the differential regulation of the IDO gene by IFNs may be the result of different interactions of proteins with the regulatory sequences of the IDO gene. The IDO gene has been mapped to chromosome 8.

• Research Organization: Indiana Univ. Foundation, Bloomington, IN (United States)
• OSTI ID: 7035382
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
CHROMOSOMES
ENZYMES
GENE REGULATION
GENETIC MAPPING
GROWTH FACTORS
HUMAN CHROMOSOME 8
HUMAN CHROMOSOMES
LYMPHOKINES
MAPPING
MITOGENS
ORGANIC COMPOUNDS
OXIDOREDUCTASES
OXYGENASES
PROTEINS