Heme synthesis in normal mouse liver and mouse liver tumors
- Univ. of Texas M. D. Anderson Cancer Center, Houston (USA)
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.
- OSTI ID:
- 6975412
- Journal Information:
- Cancer Research; (USA), Vol. 50:8; ISSN 0008-5472
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
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