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BLEOMYCIN PULMONARY TOXICITY.

TOM, WAI-MING.

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BLEOMYCIN PULMONARY TOXICITY.

Record Type:	Electronic resources : Monograph/item
Title/Author:	BLEOMYCIN PULMONARY TOXICITY./
Author:	TOM, WAI-MING.
Description:	143 p.
Notes:	Source: Dissertation Abstracts International, Volume: 41-11, Section: B, page: 4084.
Contained By:	Dissertation Abstracts International41-11B.
Subject:	Health Sciences, Pharmacology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=8109516

BLEOMYCIN PULMONARY TOXICITY.
TOM, WAI-MING.

BLEOMYCIN PULMONARY TOXICITY. - 143 p.

Source: Dissertation Abstracts International, Volume: 41-11, Section: B, page: 4084.

Thesis (Ph.D.)--University of Minnesota, 1980.

Bleomycin, a unique glycopeptide antibiotic, is effective against squamous cell carcinoma, malignant lymphoma and malignant testicular carcinoma, particularly when used in combination with other antineoplastic agents and radiotherapy. However, the severe dose-related pulmonary toxicity has limited the clinical use of this drug.Subjects--Topical Terms:

1017717
Health Sciences, Pharmacology.

BLEOMYCIN PULMONARY TOXICITY.
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035 $a AAI8109516
040 $a UnM $c UnM
100 1 $a TOM, WAI-MING. $3 1901627
245 1 0 $a BLEOMYCIN PULMONARY TOXICITY.
300 $a 143 p.
500 $a Source: Dissertation Abstracts International, Volume: 41-11, Section: B, page: 4084.
502 $a Thesis (Ph.D.)--University of Minnesota, 1980.
520 $a Bleomycin, a unique glycopeptide antibiotic, is effective against squamous cell carcinoma, malignant lymphoma and malignant testicular carcinoma, particularly when used in combination with other antineoplastic agents and radiotherapy. However, the severe dose-related pulmonary toxicity has limited the clinical use of this drug.
520 $a It is unclear whether the determining factor of bleomycin toxicity is preferential bleomycin distribution in the lung. To examine this, the disposition of bleomycin in rats has been studied with the application of a rapid and sensitive radioimmunoassay. Pharmacokinetics, organ distribution and tissue affinity studies do not support this mechanism.
520 $a To investigate the underlying mechanisms of bleomycin-induced pulmonary toxicity, an experimental model has been established in rats by repeated administration of bleomycin (5 units, twice weekly) for up to 6 weeks. Morphologically, this model has satisfied the requirements for pulmonary fibrosis: interstitial cellular infiltration, edema and spithelial proliferation with gradual progression to fibrosis. Biochemically, an increase in lung collagen content with concomitant elevation of in vivo activity of prolyl hydroxylase, a rate-limiting enzyme in collagen biosynthesis, has been confirmed. Furthermore, the observation of the direct stimulation of prolyl hydroxylase by very low concentrations of bleomycin (1-10 (mu)M) strongly suggests that the mechanism of fibrogenesis may be related to direct enzymatic alterations resulting from bleomycin. The occurrence of fibrosis is also accompanied by a depression in glucose metabolism which may be related to massive edema and increased collagen deposition.
520 $a Lung angiotensin converting enzyme activity has been evaluated as a possible indication of initial endothelial damage. This activity is unchanged until 6 weeks at which time a 59% decrease in activity is observed. The lack of correlation between severity of pulmonary edema and inhibition of enzyme activity suggests that the early endothelial damage does not affect angiotensin converting enzyme predicably.
520 $a Pulmonary microsomal lipid peroxidation, hydrogen peroxide generation and cytochrome P-450 dependent benzphetamine N-demethylation have been shown to be minimally affected. However, in the liver, which is not susceptible to bleomycin toxicity, these oxidative reactions are highly sensitive to bleomycin treatments. Concurrent stimulation of hepatic microsomal lipid peroxidation and inhibition of mixed-function oxidation suggests that these changes may indeed be related to a free radical mechanism. It may be of considerable importance that, unlike the liver, the lung consists of over forty cell types. Thus it is possible that only a small population of specific lung cells are susceptible to bleomycin damage and therefore alterations in oxidative metabolism in these damaged cells may not be easily detected.
520 $a Finally, effective clinical treatment is not available for bleomycin pulmonary toxicity, these studies strongly suggest that reversal of the bleomycin effect on subcellular collagen metabolism may be a rational and productive approach to this important problem.
590 $a School code: 0130.
650 4 $a Health Sciences, Pharmacology. $3 1017717
690 $a 0419
710 2 0 $a University of Minnesota. $3 676231
773 0 $t Dissertation Abstracts International $g 41-11B.
790 $a 0130
791 $a Ph.D.
792 $a 1980
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=8109516