Combination of nicotinamide and hyperthermia to eliminate radioresistant chronically and acutely hypoxic tumor cells

Journal Article · Sat Dec 01 04:00:00 EST 1990 · Cancer Research; (USA)

OSTI ID:6227154

Horsman, M R; Chaplin, D J; Overgaard, J ^[1]

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1. Danish Cancer Society, Aarhus (Denmark)

The interaction among nicotinamide, radiation, and heat was studied in vivo using a C3H mouse mammary carcinoma grown in the feet of CDF1 mice. Response following local tumor treatment was assessed by tumor control and regrowth delay. Nicotinamide (1000 mg/kg i.p.) produced maximal radiosensitization when injected 30 min to 2 h before irradiation (enhancement ratios (ERs), 1.2-1.5). Radiation damage was also increased by heating tumors (43.5 degrees C for 60 min) 4 h after irradiation (ERs = 1.6-2.6). This combined radiation and heat treatment was enhanced by nicotinamide but the effect depended on the assay procedure, such that although a significant increase was observed with the tumor control assay, only a slight increase was seen using regrowth delay as the end point. The development of moist desquamation in normal feet was used to estimate skin damage after irradiation. Nicotinamide and heat both resulted in a small yet significant increase in skin damage (ERs less than 1.2 and 1.1, respectively). A combined treatment resulted in a greater ER of 1.7, but when compared to the tumor response it still gave a therapeutic gain. A histological fluorescent staining technique was used to assess functional tumor vasculature at two periods in time separated by 20 min. Under normal conditions 7.7% of the vessels in this tumor were functional at one time but not the other. This value was reduced to 2.8% after nicotinamide administration. Since these fluctuations in blood flow can result in acute hypoxia we conclude that while heat eliminates chronically hypoxic tumor cells, nicotinamide probably removes the presence of acute hypoxia.

• OSTI ID: 6227154
• Journal Information: Cancer Research; (USA), Journal Name: Cancer Research; (USA) Vol. 50:23; ISSN 0008-5472; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMIDES
ANIMAL CELLS
ANIMALS
ANOXIA
AZINES
BLOOD FLOW
BODY
BODY TEMPERATURE
CARCINOMAS
DISEASES
DOSE-RESPONSE RELATIONSHIPS
EXPERIMENTAL NEOPLASMS
GLANDS
HETEROCYCLIC COMPOUNDS
HYPERTHERMIA
MAMMALS
MAMMARY GLANDS
MICE
NEOPLASMS
NICOTINAMIDE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIDINES
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RODENTS
TUMOR CELLS
VERTEBRATES
VITAMIN B GROUP
VITAMINS