Combined topical use of difluoromethyl ornithine and methylglyoxal bis (guanylhydrazone) in UV‐irradiated mouse skin

Topical application of difluoromethyl ornithine, an irreversible inhibitor of ornithine decar‐boxylase, on UV‐irradiated mouse skin, reduced epidermal putrescine and spermidine contents and greatly enhanced the epidermal uptake of subsequently applied methylglyoxal bis(guanyl‐hydrazone). High epidermal concentrations of methylglyoxal bis (guanylhydrazone) could effectively be lowered by a single application of an ointment containing spermidine. The present results indicate that difluoromethylornithine and methylglyoxal bis (guanylhydrazone) pene trate mammalian skin from topical ointments, and that, in case of a too high (toxic) methylglyoxal bis (guanylhydrazone) concentration, spermidine can be used as a ‘rescuing’ agent.

[1]  J. Jänne,et al.  Effect of epidermal polyamine depletion on the accumulation of methylglyoxal bis(guanylhydrazone) in mouse skin. , 1982, The Journal of investigative dermatology.

[2]  M. Siimes,et al.  Use of polyamine antimetabolites in experimental tumours and in human leukemia. , 1981, Medical biology.

[3]  M. Siimes,et al.  Synergistic action of two polyamine antimetabolites leads to a rapid therapeutic response in childhood leukemia , 1981, International journal of cancer.

[4]  J. Lauharanta,et al.  Reduction of increased polyamine levels in psoriatic lesions by retinoid and PUVA treatments , 1981, The British journal of dermatology.

[5]  P. Schechter,et al.  Comparative effects of topical anthralin and difluoromethylornithine (αDFMO) on epidermal polyamine concentration in psoriasis , 1981, The British journal of dermatology.

[6]  J. S. Taylor,et al.  A clinical screening program for topical chemotherapeutic drugs in psoriasis. , 1981, Archives of dermatology.

[7]  P. Seppänen,et al.  Polyamine deprivation-induced enhanced uptake of methylglyoxal bis(guanylhydrazone) by tumor cells. , 1981, Biochimica et biophysica acta.

[8]  P. Seppänen,et al.  Intracellular putrescine and spermidine deprivation induces increased uptake of the natural polyamines and methylglyoxal bis(guanylhydrazone). , 1980, The Biochemical journal.

[9]  N. Lowe.  Epidermal ornithine decarboxylase, polyamines, cell proliferation, and tumor promotion. , 1980, Archives of dermatology.

[10]  P. Schechter,et al.  [Polyamines in psoriasis]. , 1980, Annales de dermatologie et de venereologie.

[11]  P. Seppänen,et al.  Sensitive Enzymic determination of methylglyoxal bis(guanylhydrazone) in cultured cells and in animal tissues , 1980, FEBS letters.

[12]  N. Seiler,et al.  Effects of ultraviolet light on epidermal polyamine metabolism. , 1979, Biochemical medicine.

[13]  A. Verma,et al.  Ultraviolet light induces epidermal ornithine decarboxylase activity. , 1978, The Journal of investigative dermatology.

[14]  J. Voorhees,et al.  Glucocorticoid inhibits elevated polyamine biosynthesis in psoriasis. , 1978, The Journal of investigative dermatology.

[15]  J. Koch-weser,et al.  Skin polyamine levels in psoriasis: the effect of dithranol therapy * , 1978, European journal of clinical investigation.

[16]  B. Metcalf,et al.  Catalytic irreversible inhibition of mammalian ornithine decarboxylase (E.C.4.1.1.17) by substrate and product analogs , 1978 .

[17]  T. Slaga,et al.  Phorbol esters stimulate DNA synthesis and ornithine decarboxylase activity in mouse epidermal cell cultures , 1976, Nature.

[18]  R. Boutwell,et al.  Induction of the polyamine-biosynthetic enzymes in mouse epidermis and their specificity for tumor promotion. , 1975, Cancer research.

[19]  A. Harell,et al.  Determination of polyamines in urine. , 1973, Clinica chimica acta; international journal of clinical chemistry.

[20]  A. Pegg,et al.  Paradoxical enhancement of S-adenosylmethionine decarboxylase in rat tissues following administration of the specific inhibitor methyl glyoxal bis(guanylhydrazone). , 1973, Biochemical and biophysical research communications.

[21]  A. Schenone,et al.  Separation of two proteins required for synthesis of spermidine from S-adenosyl-L-methionine and putrescine in rat prostate. , 1971, Biochemical and biophysical research communications.

[22]  J. Jänne,et al.  Dissociation of putrescine-activated decarboxylation of S-adenosyl-L-methionine from the enzymic synthesis of spermidine and spermine by purified prostatic enzyme preparations. , 1971, Biochemical and biophysical research communications.

[23]  N. Seiler.  Use of the dansyl reaction in biochemical analysis. , 2006, Methods of biochemical analysis.

[24]  A. Pegg,et al.  On the role of S-adenosyl-L-methionine in the biosynthesis of spermidine by rat prostate. , 1969, The Journal of biological chemistry.

[25]  K. W. GILES,et al.  An Improved Diphenylamine Method for the Estimation of Deoxyribonucleic Acid , 1965, Nature.

[26]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.