Inhibition of Initiation and Promotion Steps of Carcinogenesis by Glucose-6-Phosphate Dehydrogenase Deficiency

  • Francesco Feo
  • Renato Garcea
  • Lucia Daino
  • Serenella Frassetto
  • Patrizia Cozzolino
  • Maria E. Ruggiu
  • Maria G. Vannini
  • Rosa Pascale
  • Luciano Lenzerini
  • Maria M. Simile
  • Marco Puddu

Abstract

A number of observations indicate that deficiency of glucose-6-phosphate dehydrogenase (G6PD), either genetically transmitted or caused by dehydroepiandrosterone (DHEA)1, or some related steroids, is associated with an antitumor effect. Some epidemiologial evidence of a decreased tumor incidence in G6PD-deficient subjects has been reported2–5. Although these observations, do not definitively prove the existence of clear relationships between G6PD-deficiency and tumor incidence, they suggest a negative correlation. In accordance with this hypothesis retrospective studies have shown subnormal plasma levels of DHEA or DHEA-sulfate in women with breast cancer6,7. Moreover, in a prospective study a subnormal urinary excretion of the DHEA metabolites androsterone and etiocholanolone has been found to be associated with enhanced breast cancer risk8. DHEA mimics many of the effects of the genetically transmitted G6PD deficiency as concerns the resistance of in vitro cultured cells to the toxic and transforming effects of carcinogens. Following the first observation by Schwartz9 that long-term per os treatment with DHEA inhibits the formation of spontaneous tumors in mice, different other studies have shown that this treatment also prevents the development of chemically induced tumors in the same animal10–13, as well as in the rat14. DHEA is known to exhibit an anti-obesity effect (cf. ref. 15 for review). Even if in some rat strains DHEA causes a decrease in food intake, it has been suggested that the anti-obesity effect is linked to a decreased food utilization more than to a reduced intake16. Alternatively, an increased ß-oxidation of fatty acids in peroxisomes, could represent an “energy wasting” pathway in DHEA-treated animals17. Reduction in food intake is known to decrease the susceptibility of different tissues to cancer18. However, the possibility that the DHEA anti-tumor action is linked to food restriction, is ruled out by the observation that topic application of DHEA, while not reducing body weight, greatly inhibits development of skin tumor in mice12.

Keywords

Malic Enzyme G6PD Deficiency Dehydrogenase Deficiency G6PD Activity Related Steroid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Francesco Feo
    • 1
  • Renato Garcea
    • 1
  • Lucia Daino
    • 1
  • Serenella Frassetto
    • 1
  • Patrizia Cozzolino
    • 1
  • Maria E. Ruggiu
    • 1
  • Maria G. Vannini
    • 1
  • Rosa Pascale
    • 1
  • Luciano Lenzerini
    • 1
  • Maria M. Simile
    • 1
  • Marco Puddu
    • 1
  1. 1.Istituto di Patologia generaleUniversità di SassariSassariItaly

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