Genotypesa | Cyp1(+/+), Cyp1b1(−/−) | Cyp1a1(−/−) | Cyp1a1/1b1(−/−) |
---|---|---|---|
Clinical outcome | Healthy for lifetime | Adenocarcinoma of PSI (at 8-12 wk) | Squamous cell carcinoma of preputial gland duct (at 8–12 wk) |
Blood BaP levels (ng/ml)b | ∼0.1 | ∼4 | ∼13 |
ALT, AST, hemoglobin, hematocrit, methemoglobin levels | Normalb | Borderline abnormalb | Normalb |
Bone marrow, spleenb | Normal | Slight hypocellularity | Normal |
Liver, thymusb | Normal | AHR activationc | AHR activationc |
↵a Knockout genotype in all lines was backcrossed into C57BL/6J (B6) mice at least 8 times, rendering all animals with >99.8% B6 genetic background; hence, B6 inbred mice were used as Cyp1(+/+) controls. These data are summarized from Shi et al. (2010b) and Gálvez-Peralta et al. (2013).
↵b Measured after 12.5 mg/kg/d oral BaP for 4 weeks. Abbreviations are the same as in Table 2.
↵c Activation reflects the fact that daily BaP treatment causes chronic AHR activation, which in turn leads to proliferation of the endoplasmic reticulum and increased liver weight and thymus weight; these effects are AHR-dependent but are independent of CYP1 metabolism (Uno et al., 2006).