A mathematical approach to benzo[a]pyrene-induced hematotoxicity
- 29 Downloads
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 wordsBenzo[a]pyrene Mathematical model Hematopoiesis
Unable to display preview. Download preview PDF.
- International Agency for Research on Cancer (1983) IARC Monographs on the evaluation of the carcinogenic risk of chemicals to humans. Polynuclear aromatic compounds. Part I: Chemical, environmental, and experimental data, 32: 34–91Google Scholar
- Loeffler M, Wichmann HE, Jarczyk AJ (1985) Chronic irradiation — a model analysis. In: Wichmann HE, Loeffler M (eds) Mathematical modeling of cell proliferation. Stem cell regulation in hemopoiesis, vol 1. CRC Press, Boca Raton, Fl, pp 139–146Google Scholar
- Nebert DW (1989) The Ah locus: genetic differences in toxicity, cancer, mutation, and birth defects. CRC Crit Rev Toxicol 20 : 153–74Google Scholar
- Scheding S, Loeffler M, Schmitz S, Seidel HJ, Wichmann HE (1992) Hematotoxic effects of benzene analyzed by methematical modeling. Toxicology (in press)Google Scholar
- Wichmann HE, Loeffler M (1985) Mathematical modeling of cell proliferation. Stem cell regulation in hemopoiesis, vols 1 and 2. CRC Press, Boca Raton, FLGoogle Scholar