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Figure 1.

Metabolism of benzo(a)pyrene in Apc+/+ and ApcMin/+ cell lines.

Typical radio-HPLC profiles of supernatants obtained from incubation of 3 µM [14C]-B(a)P with (A) Apc+/+ and (B) ApcMin/+ cell lines (incubation time: 24 h).

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Table 1.

Production of B(a)P metabolites (supernatants and cell extracts) on Apc+/+ and ApcMin/+ cell lines after 24 h incubations with 3 µM [14C]-B(a)P.

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Figure 2.

Genotoxicity of B(a)P in Apc+/+ and ApcMin/+ cell lines.

Apc+/+ and ApcMin/+ cells were treated with the indicated concentrations of BaP for 24 h. (A) Genotoxicity was evaluated by HPLC-MS/MS quantification of dG-N2-BPDE in DNA. (B) Genotoxicity was evaluated with γHAX ICW assay. Bars represent the average of at least three independent experiments with SEM. Statistically significant increase in H2AX phosphorylation compared with DMSO control using Student’s test; *, p<0.05; **, p<0.01. Statistically significant difference between Apc+/+ and ApcMin/+ cells using Student’s test; b, p<0.05; a, p<0.01.

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Table 2.

Genotoxicity and cytotoxicity of B(a)P and PhIP in Apc+/+ and ApcMin/+ cell lines.

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Figure 3.

Genotoxicity of PhIP in Apc+/+ and ApcMin/+ cell lines.

Apc+/+ and ApcMin/+ cells were treated with the indicated concentrations of PhIP for 24 h. (A) Genotoxicity was evaluated by HPLC-MS/MS quantification of dG-C8-PhIP in DNA. (B) Genotoxicity was evaluated with γHAX ICW assay. Bars represent the average of at least three independent experiments with SEM. Statistically significant increase in H2AX phosphorylation compared with DMSO control using Student’s test; *, p<0.05; **, p<0.01. Statistically significant difference between Apc+/+ and ApcMin/+ cells using Student’s test; b, p<0.05; a, p<0.01.

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Figure 4.

Synergic genotoxicity of B(a)P and PhIP in Apc+/+ and ApcMin/+ cell lines.

Apc+/+ and ApcMin/+ cells were treated with the indicated concentrations of BaP and PhIP for 24 h. (A) Genotoxicity was evaluated by quantification by HPLC-MS/MS quantification of B(a)P- and PhIP-derived DNA adducts. (B) Genotoxicity was evaluated with γHAX ICW assay. Bars represent the average of at least three independent experiments with SEM. Statistically significant increase in H2AX phosphorylation compared with DMSO control using Student’s test; **, p<0.01. Statistically difference between single and combined treatment using Student’s test; ns, not significant; a, p<0.01.

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