Effect of 5-azacytidine and cortisol on the P1798 cortisol-sensitive and non-resistant lymphosarcoma

Thesis/Dissertation · Wed Jan 01 00:00:00 EST 1986

OSTI ID:5556682

Chi, C

The P1798 lymphosarcoma is a tumor with both cortisol-sensitive (CS) and cortisol-resistant (CR) lines. Although differences between the CS and CR cells have been reported, none can fully explain the detailed mechanism of glucocorticoid resistance in CR tumors. Recently, it was shown that 5-azacytidine treatment could generate CS cells from CR SAK lymphoma cells in vitro. The present study examined the effect of combination treatment with 5-azacytidine and cortisol on the growth of the P1798 lymphosarcoma. 5-Azacytidine rendered the P1798 CR tumors partially cortisol-sensitive, and enhanced the cortisol-induced regression of the P1798 CS tumors. Survival of mice bearing both CS and CR P1798 tumors was increased by combination treatment. Similar whole cell and nuclear binding of /sup 3/H-TA were observed in both 5-azacytidine-treated and control P1798 tumors. However, CR nuclei retained 64% of the whole cell binding of /sup 3/H-TA compared to 25-29% nuclear retention in CS tumors. DNA methylation in tumors from 5-azacytidine-treated mice decreased to 53% (CS) and 42% (CR) of control. Since 5-azacytidine did not result in any change in thymidine labeling index or cell cycle distribution in P1798 tumors, it would appear to be cytostatic rather than cytotoxic to P1798 tumors. Three cell lines have been isolated from the P1798 lymphosarcoma: two are cortisol-sensitive both in vivo and in vitro, while the other is cortisol-resistant. Results from this study suggest that glucocorticoid resistance is a reversible process, and that the effect of 5-azacytidine on the P1798 CR tumor is at the gene expression level.

• Research Organization: State Univ. of New York, Buffalo (USA)
• OSTI ID: 5556682
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANTIMETABOLITES
BIOLOGICAL EFFECTS
HYDROCORTISONE
LYMPHOSARCOMAS
SENSITIVITY
GENETICS
GLUCOCORTICOIDS
GROWTH
IN VIVO
MICE
RECEPTORS
THYMIDINE
TRITIUM COMPOUNDS
ADRENAL HORMONES
ANIMALS
AZINES
BIOLOGY
CORTICOSTEROIDS
DISEASES
DRUGS
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROXY COMPOUNDS
KETONES
LABELLED COMPOUNDS
LYMPHOMAS
MAMMALS
MEMBRANE PROTEINS
NEOPLASMS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PREGNANES
PROTEINS
PYRIMIDINES
RIBOSIDES
RODENTS
SARCOMAS
STEROID HORMONES
STEROIDS
VERTEBRATES
551001* - Physiological Systems- Tracer Techniques