Inhibition of DNA and protein synthesis in UV-irradiated mouse skin by 2-difluoromethylornithine, methylglyoxal bis(guanylhydrazone), and their combination

Journal Article · Mon Aug 01 04:00:00 EDT 1983 · J. Invest. Dermatol.; (United States)

DOI:https://doi.org/10.1111/1523-1747.ep12542177· OSTI ID:5545719

Kaepyaho, K; Lauharanta, J; Jaenne, J

Exposure of mouse skin to UVB irradiation greatly enhanced the biosynthesis and accumulation of putrescine and spermidine before or concomitantly with stimulation of epidermal macromolecular (DNA and protein) synthesis. Topical treatment of UV-exposed skin with 2 inhibitors of polyamine biosynthesis, 2-difluoromethylornithine (DFMO) and methylglyoxal bis(guanylhydrazone) (MGBG) prevented the enhanced epidermal accumulation of polyamines, especially spermidine, and also inhibited the incorporation of radioactive precursors into DNA and protein. When applied in combination, these 2 antimetabolites of polyamines produced an inhibition of macromolecular synthesis that was at least additive: (/sup 3/H)thymidine incorporation decreased by 80% and (/sup 14/C)leucine incorporation by 44% as compared with the UVB-irradiated control mice. A slight decrease in the ratio of (/sup 3/H)histidine/(/sup 14/C)leucine incorporation indicated that protein synthesis of the differentiating cell layers was also affected by the inhibitors. The effects of the combined DFMO and MGBG treatment were partially reversed by concomitant topical application of spermidine.

• Research Organization: Department of Biochemistry, University of Helsinki, Finland
• OSTI ID: 5545719
• Journal Information: J. Invest. Dermatol.; (United States), Journal Name: J. Invest. Dermatol.; (United States) Vol. 81:2; ISSN JIDEA
• Country of Publication: United States
• Language: English

Related Subjects

560114* -- Radiation Effects on Biochemicals-- In Animals-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
AMINO ACIDS
ANIMALS
ANTIMETABOLITES
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOSYNTHESIS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
DNA
DNA REPLICATION
DRUGS
ELECTROMAGNETIC RADIATION
HETEROCYCLIC COMPOUNDS
INHIBITION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LEUCINE
MAMMALS
MICE
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
ORNITHINE
PROTEINS
PUTRESCINE
PYRIMIDINES
RADIATION EFFECTS
RADIATIONS
RIBOSIDES
RODENTS
SKIN
SPERMIDINE
SYNTHESIS
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ULTRAVIOLET RADIATION
VERTEBRATES