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Title: Heme synthesis in normal mouse liver and mouse liver tumors

Abstract

Hepatic cancers from mice and rats demonstrate decreased levels of delta-aminolevulinic acid synthase, the rate-limiting enzyme in the heme synthetic pathway, and increased heme oxygenase, the heme-catabolizing enzyme. These findings suggest that diminution of P-450, b5, and catalase in these lesions may result from a heme supply that is limited by decreased heme synthesis and increased heme catabolism. Heme synthesis was measured in mouse liver tumors (MLT) and adjacent tumor-free lobes (BKG) by administering the radiolabeled heme precursors {sup 55}FeCl3 and (2-{sup 14}C)glycine and subsequently extracting the heme for determination of specific activity. Despite reduced delta-aminolevulinic acid synthase activity in MLT, both tissues incorporated (2-14C)glycine into heme at similar rates. At early time points, heme extracted from MLT contained less 55Fe than that from BKG. This was attributed to the findings that MLT took up 55Fe at a slower rate than BKG and had larger iron stores than BKG. The amount of heme per milligram of protein was also similar in both tissues. These findings militate against the hypothesis that diminished hemoprotein levels in MLT result from limited availability of heme. It is probable, therefore, that decreased hemoprotein levels in hepatic tumors are linked to a general program of dedifferentiationmore » associated with the cancer phenotype. Diminution of hemoprotein in MLT may result in a relatively increased intracellular heme pool. delta-Aminolevulinic acid synthase and heme oxygenase are, respectively, negatively and positively regulated by heme. Thus, their alteration in MLT may be due to the regulatory influences of the heme pool.« less

Authors:
;  [1]
  1. Univ. of Texas M. D. Anderson Cancer Center, Houston (USA)
Publication Date:
OSTI Identifier:
6975412
Resource Type:
Journal Article
Journal Name:
Cancer Research; (USA)
Additional Journal Information:
Journal Volume: 50:8; Journal ID: ISSN 0008-5472
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; HEME; BIOSYNTHESIS; LIVER; NEOPLASMS; PATHOGENESIS; CARBON 14 COMPOUNDS; GLYCINE; IRON 55; LYASES; MICE; OXYGENASES; PORPHYRINS; TRACER TECHNIQUES; AMINO ACIDS; ANIMALS; BETA DECAY RADIOISOTOPES; BODY; CARBOXYLIC ACIDS; DIGESTIVE SYSTEM; DISEASES; ELECTRON CAPTURE RADIOISOTOPES; ENZYMES; EVEN-ODD NUCLEI; GLANDS; HETEROCYCLIC ACIDS; HETEROCYCLIC COMPOUNDS; INTERMEDIATE MASS NUCLEI; IRON ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; LABELLED COMPOUNDS; MAMMALS; NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; OXIDOREDUCTASES; PIGMENTS; RADIOISOTOPES; RODENTS; SYNTHESIS; VERTEBRATES; YEARS LIVING RADIOISOTOPES; 550901* - Pathology- Tracer Techniques

Citation Formats

Stout, D L, and Becker, F F. Heme synthesis in normal mouse liver and mouse liver tumors. United States: N. p., 1990. Web.
Stout, D L, & Becker, F F. Heme synthesis in normal mouse liver and mouse liver tumors. United States.
Stout, D L, and Becker, F F. 1990. "Heme synthesis in normal mouse liver and mouse liver tumors". United States.
@article{osti_6975412,
title = {Heme synthesis in normal mouse liver and mouse liver tumors},
author = {Stout, D L and Becker, F F},
abstractNote = {Hepatic cancers from mice and rats demonstrate decreased levels of delta-aminolevulinic acid synthase, the rate-limiting enzyme in the heme synthetic pathway, and increased heme oxygenase, the heme-catabolizing enzyme. These findings suggest that diminution of P-450, b5, and catalase in these lesions may result from a heme supply that is limited by decreased heme synthesis and increased heme catabolism. Heme synthesis was measured in mouse liver tumors (MLT) and adjacent tumor-free lobes (BKG) by administering the radiolabeled heme precursors {sup 55}FeCl3 and (2-{sup 14}C)glycine and subsequently extracting the heme for determination of specific activity. Despite reduced delta-aminolevulinic acid synthase activity in MLT, both tissues incorporated (2-14C)glycine into heme at similar rates. At early time points, heme extracted from MLT contained less 55Fe than that from BKG. This was attributed to the findings that MLT took up 55Fe at a slower rate than BKG and had larger iron stores than BKG. The amount of heme per milligram of protein was also similar in both tissues. These findings militate against the hypothesis that diminished hemoprotein levels in MLT result from limited availability of heme. It is probable, therefore, that decreased hemoprotein levels in hepatic tumors are linked to a general program of dedifferentiation associated with the cancer phenotype. Diminution of hemoprotein in MLT may result in a relatively increased intracellular heme pool. delta-Aminolevulinic acid synthase and heme oxygenase are, respectively, negatively and positively regulated by heme. Thus, their alteration in MLT may be due to the regulatory influences of the heme pool.},
doi = {},
url = {https://www.osti.gov/biblio/6975412}, journal = {Cancer Research; (USA)},
issn = {0008-5472},
number = ,
volume = 50:8,
place = {United States},
year = {Sun Apr 15 00:00:00 EDT 1990},
month = {Sun Apr 15 00:00:00 EDT 1990}
}