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Archives of Toxicology

, Volume 66, Issue 8, pp 546–550 | Cite as

A mathematical approach to benzo[a]pyrene-induced hematotoxicity

  • Stefan Scheding
  • Markus Loeffler
  • Volker Anselstetter
  • H. -Erich Wichmann
Original Investigations

Abstract

Benzo[a]pyrene (BaP) has been reported to exert a differential effect on murine hematopoiesis that is mouse strain specific. Interpretation of these results based solely on experimental data is restricted and leaves important questions unanswered. Therefore, a mathematical model of murine hematopoiesis was applied in order to: (1) identify the targets of BaP, (2) quantify the damage to target cells and (3) based on these results, interpret differences in strain susceptibility. Model analysis of the hematopoietic response of D2 and BDF1 mice to a daily oral administration of 125 mg/kg BaP showed that proliferating hematopoietic cells are the targets of BaP. Within this group it was found that: (a) erythropoietic cells were the most susceptible to BaP, (b) granulopoietic cells showed a susceptibility half that of erythropoietic cells and (c) the susceptibility of stem cells ranged between that of erythropoietic and granulopoietic cells. This damage pattern was the same for both strains, indicating that the difference between the strains was quantitative. As cell destruction rates were about 3-fold higher for D2 than BDF1 mice, it was concluded that D2 mice were about three times as susceptible to BaP as BDF1 mice. The study showed that the mathematical model, in addition to experimental methods, provided an efficient tool for the analysis of BaP hematotoxicity.

Key words

Benzo[a]pyrene Mathematical model Hematopoiesis 

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Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Stefan Scheding
    • 1
    • 2
  • Markus Loeffler
    • 2
  • Volker Anselstetter
    • 3
  • H. -Erich Wichmann
    • 1
    • 4
  1. 1.Department of Labor Safety and Environmental MedicineUniversity of WuppertalWuppertal 1Federal Republic of Germany
  2. 2.Clinic I of Internal Medicine, Department of BiometryUniversity of CologneKöln 41Federal Republic of Germany
  3. 3.Department of Internal Medicine, Division of Hematology and OncologyUniversity of UlmUlmFederal Republic of Germany
  4. 4.Institute of EpidemiologyGSFNeuherbergFederal Republic of Germany

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