Ultrastructural evidence of cardiac damage resulting from thoracic irradiation and anthracyclines in the rat

Conference · Wed Aug 01 04:00:00 EDT 1984 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

OSTI ID:6407703

Kimler, B F; Mansfield, C M; Svoboda, D J; Cox, G G

The effects of radiation combined with Adriamycin (ADR) or Dihydroxyanthraquinone (DHAQ, NSC 279836) on the induction of cardiomyopathy in the rat were investigated using electron microscopy. Rats were treated with ADR or DHAQ at 2.5, 5.0, or 10 mg/kg ip; thoracic irradiation at 12, 15, 18, 21, or 24 Gy of 25 MV x rays; or a combination of either drug at 5.0 mg/kg plus 15 Gy x rays. Survival times were observed to be linear, inverse functions of the dose of drug or radiation received. Combinations of ADR plus radiation produced an increased lethality while the combination of DHAQ and radiation produced similar lethality as DHAQ alone. Electron microscopic examination of cardiac tissues demonstrated dramatic decreases in mitochondrial number and destruction of mitochondrial structure. These results indicate that electron microscopy can be used to document cellular changes that may only be functionally expressed as long-term normal tissue damage or animal lethality. The finding that DHAQ can produce significant cardiotoxicity, and that this cardiotoxicity is enhanced by concomitant thoracic irradiation, suggest caution while this drug is being investigated for clinical use.

• Research Organization: Univ. of Kansas Medical Center, Kansas City
• OSTI ID: 6407703
• Report Number(s): CONF-8311204-
• Conference Information: Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Journal Volume: 10:8
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTHRAQUINONES
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTINEOPLASTIC DRUGS
AROMATICS
BODY
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
DOXORUBICIN
DRUGS
DYES
ELECTROMAGNETIC RADIATION
ELECTRON MICROSCOPY
EXTERNAL IRRADIATION
HEART
HYDROXY COMPOUNDS
IONIZING RADIATIONS
IRRADIATION
MAMMALS
MICROSCOPY
MITOCHONDRIA
MORPHOLOGICAL CHANGES
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
ORGANS
PARTIAL BODY IRRADIATION
QUINIZARIN
QUINONES
RADIATIONS
RADIOSENSITIVITY EFFECTS
RATS
RODENTS
TOXICITY
TRANSMISSION ELECTRON MICROSCOPY
ULTRASTRUCTURAL CHANGES
VERTEBRATES
X RADIATION