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Assessment of normal rat lung damage following radiotherapy-chemotherapy
1400
(92)
Radiation Oncology
ASSESSMENT
??Biology ??Physics
October 1980, Volume 6, Number 10
OF NORMAL RAT LUNG DAMAGE FOLLOWING RADIOTHERAPY-CHEMOTHERAPY Carl M. Mansfield, M.Dll Bruce F. Kimler, Ph.D. 2 Tribhawan S. Vats, M.D Donald J. Svoboda, M.D13 Sheri D. Henderson, Ph.D.l
1
Radiation Bioloqy Laboratory *Department of Radiation Therapy 3Department of Pediatrics Department of Pathology University of Kansas Medical Center Kansas City, KS 66103 As more cancer patients display an extended survival brought about through the use of combined modality therapy, there is an increased concern with the effects of these therapeutic schedules on normal tissues. In order to provide information predictive to the clinical situation, we have evaluated the effects of ionizing radiation and cancer chemotherapeutic agents, singly and in combination, on lung structure and function in rats. Animals received a single ip injection of either balanced saline only, Adriamycin (1.0 mg/kg), Bleomycin (10 mg/kg), or Dihydroxyanthraauinone Animals either received no further treatment; or else (DHAQ, 3.0 mg/kg). received 25 MV X-rays to the thoracic cavity (12 Gy) at 0, 1.5, 3, or 6 The development of normal tissue damage was months after chemotherapy. In addition, phvsiomonitored first by the endpoint of animal survival. logical changes in lung function were monitored using a mercury gauge Biochemical changes were monitored by (chest expansion) respirometer. assay of serum and tissue levels of angiotensin-l-converting enzyme. Histological examinations were conducted on animals that had either died The data are or had been'sacrificed at specific times after treatment. being correlated so as to assess microscopic changes in lung structure in relation to alterations in lung function following combined modality To date (9 months after initial treatment), the following treatment. No appreciable lethality has been observed ohenomena have been observed. except in rats that received DHAQ (19/56 dead). No differences have been observed in weight gain between groups. Aooroximately 40% of those rats treated with DHAQ have developed abdominal abcesses at the site of No significant differences have been injection (due to extravasation). detected in lung function as monitored by respirometer. Histological examination has revealed a suggestion of fibrosis at 3 months for all rats that received X-ray. Of the drugs, only Bleomycin produced consistent These and subsequent findings will hopefully serve as guidelines fibrosis. to oredict and prevent long-term pulmonary deficit in patients treated for cancer with a combined modality approach that includes chemotherapy and radiation therapy to the chest.
(93)
COMPARISON
OF DIHYDROXYANTHRAQUINONE AND ADRIAMYCIN: INTERACTION WITH RADIATION IN CULTURED MAMMALIAN CELLS Bruce F. Kimler, Ph.D. Radiation Biology Laboratory Deoartment of Radiation Therapy University of Kansas Medical Center Kansas City, KS 66103
Dihydroxyanthraquinone (DHAQ) is currently being tested as a cancer chemotherapeutic agent because of its structural similarity to Adriamycin
(92)
Radiation Oncology
ASSESSMENT
??Biology ??Physics
October 1980, Volume 6, Number 10
OF NORMAL RAT LUNG DAMAGE FOLLOWING RADIOTHERAPY-CHEMOTHERAPY Carl M. Mansfield, M.Dll Bruce F. Kimler, Ph.D. 2 Tribhawan S. Vats, M.D Donald J. Svoboda, M.D13 Sheri D. Henderson, Ph.D.l
1
Radiation Bioloqy Laboratory *Department of Radiation Therapy 3Department of Pediatrics Department of Pathology University of Kansas Medical Center Kansas City, KS 66103 As more cancer patients display an extended survival brought about through the use of combined modality therapy, there is an increased concern with the effects of these therapeutic schedules on normal tissues. In order to provide information predictive to the clinical situation, we have evaluated the effects of ionizing radiation and cancer chemotherapeutic agents, singly and in combination, on lung structure and function in rats. Animals received a single ip injection of either balanced saline only, Adriamycin (1.0 mg/kg), Bleomycin (10 mg/kg), or Dihydroxyanthraauinone Animals either received no further treatment; or else (DHAQ, 3.0 mg/kg). received 25 MV X-rays to the thoracic cavity (12 Gy) at 0, 1.5, 3, or 6 The development of normal tissue damage was months after chemotherapy. In addition, phvsiomonitored first by the endpoint of animal survival. logical changes in lung function were monitored using a mercury gauge Biochemical changes were monitored by (chest expansion) respirometer. assay of serum and tissue levels of angiotensin-l-converting enzyme. Histological examinations were conducted on animals that had either died The data are or had been'sacrificed at specific times after treatment. being correlated so as to assess microscopic changes in lung structure in relation to alterations in lung function following combined modality To date (9 months after initial treatment), the following treatment. No appreciable lethality has been observed ohenomena have been observed. except in rats that received DHAQ (19/56 dead). No differences have been observed in weight gain between groups. Aooroximately 40% of those rats treated with DHAQ have developed abdominal abcesses at the site of No significant differences have been injection (due to extravasation). detected in lung function as monitored by respirometer. Histological examination has revealed a suggestion of fibrosis at 3 months for all rats that received X-ray. Of the drugs, only Bleomycin produced consistent These and subsequent findings will hopefully serve as guidelines fibrosis. to oredict and prevent long-term pulmonary deficit in patients treated for cancer with a combined modality approach that includes chemotherapy and radiation therapy to the chest.
(93)
COMPARISON
OF DIHYDROXYANTHRAQUINONE AND ADRIAMYCIN: INTERACTION WITH RADIATION IN CULTURED MAMMALIAN CELLS Bruce F. Kimler, Ph.D. Radiation Biology Laboratory Deoartment of Radiation Therapy University of Kansas Medical Center Kansas City, KS 66103
Dihydroxyanthraquinone (DHAQ) is currently being tested as a cancer chemotherapeutic agent because of its structural similarity to Adriamycin