Skip to main content

Relationships between NADPH Content and Benzo(a)pyrene Metabolism in Normal and Glucose-6-Phosphate Dehydrogenase-Deficient Human Fibroblasts

  • Chapter
Chemical Carcinogenesis

Abstract

Previous work in our laboratory has shown that human skin fibroblasts (HSF) and human lymphocytes carrying the Mediterranean variant of glucose-6-phosphate dehydrogenase (G6PD) exhibit a great decrease in hexose monophosphate shunt and in NADP /NADPH ratio1,2. G6PD deficiency protects in vitro growing HSF and lymphocytes from benzo(a)pyrene (BaP) toxicity. G6PD-deficient HSF give rise in soft agar, after incubation with BaP, to a lower number of colonies than normal HSF1. Aryl hydrocarbon hydroxylase (AHH) activities are lower in G6PD-deficient cells, when tested in the absence of exogenous NADPH2. G6PD-deficient cells, incubated in vitro with BaP, produce low amounts of organic- and water-soluble BaP metabolites and show a decreased ability to form BaP-7,8-diol-9,10-epoxide and BaP-DNA adducts3,4.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. F. Feo, L. Pirisi, R. Pascale, L. Daino, S. Frassetto and R. Garcea, Modulatory effect of glucose-6-phosphate dehydrogenase deficiency on the benzo(a)pyrene toxicity and transforming activity for in vitro cultured human skin fibroblasts, Cancer Res. 38:3419 (1984).

    Google Scholar 

  2. F. Feo, L. Pirisi, R. Pascale, L. Daino, S. Frassetto, S. Zanetti and R. Garcea, Modulatory mechanisms of chemical carcinogenesis: the role of the NADPH pool in benzo(a)pyrene activation, Toxicol. Pathol. 12:262 (1984).

    Google Scholar 

  3. L. Pirisi, R. Garcea, R. Pascale, M. E. Ruggiu and F. Feo, Control of glucose-6-phosphate dehydrogenase deficiency on the formation of mutagenic and carcinogenic metabolites derived from benzo(a)pyrene, Toxicol. Pathol. 15:115 (1987).

    Article  PubMed  CAS  Google Scholar 

  4. F. Feo, M. E. Ruggiu, L. Lenzerini, R. Garcea, L. Daino, S. Frassetto, V. Addis, L. Gaspa and R. Pascale, Benzo(a)pyrene metabolism by lymphocytes from normal individuals and individuals carrying the Mediterranean variant of glucose-6-phosphate dehydrogenase, Int. J. Cancer 39:560 (1987).

    Article  PubMed  CAS  Google Scholar 

  5. K. Rudo, S. Ellis, B. J. Bryant, K. Lawrence, G. Curtis, H. Garland and S. Nesnow, Quantitative analysis of the metabolism of benzo(a)pyrene by transformable C3H10T1/2CL8 mouse embryo fibroblasts, Teratog. Carcinog. Mutagen. 6:307 (1986).

    Article  PubMed  CAS  Google Scholar 

  6. L. A. Reinke, F. C. Kauffman, S. A. Belinsky and R. G. Thurman, Interactions between ethanol metabolism and mixed function oxidation in perfused rat liver: inhibition of p-nitroanisole O-demethylation, J. Pharmacol. Exp. Ther. 213:70 (1980).

    PubMed  CAS  Google Scholar 

  7. L. A. Reinke, P. McManus, F. C. Kauffman and R. G. Thurman, Benzo(a)-pyrene phenol production by perfused rat liver and its inhibition by ethanol, Cancer Res. 4:1681 (1982).

    Google Scholar 

  8. I. J. Sadowski, J. A. Wright and L. G. Israels, A permeabilized cell system for studying regulation of aryl hydrocarbon hydroxylase: NADPH as rate limiting factor in benzo(a)pyrene metabolism, Int. J. Biochem. 17:1025 (1985).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Springer Science+Business Media New York

About this chapter

Cite this chapter

Pascale, R. et al. (1988). Relationships between NADPH Content and Benzo(a)pyrene Metabolism in Normal and Glucose-6-Phosphate Dehydrogenase-Deficient Human Fibroblasts. In: Feo, F., Pani, P., Columbano, A., Garcea, R. (eds) Chemical Carcinogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9640-7_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-9640-7_9

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-9642-1

  • Online ISBN: 978-1-4757-9640-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics