Differences in gene expression and benzo[a]pyrene-induced DNA adduct formation in the liver of three strains of female mice with identical AhRb2 genotype treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin and/or benzo[a]pyrene
✍ Scribed by Qing Wu; Junko S. Suzuki; Hiroko Zaha; Tien-Min Lin; Richard E. Peterson; Chiharu Tohyama; Seiichiroh Ohsako
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 392 KB
- Volume
- 28
- Category
- Article
- ISSN
- 0260-437X
- DOI
- 10.1002/jat.1331
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✦ Synopsis
Abstract
To search for genes whose products modify aryl hydrocarbon receptor (AhR)‐dependent toxicity caused by 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD), gene expression profiles in the liver were surveyed using microarrays 24 h after the administration of TCDD to three strains of female mice, BALB/cAnN (BALB), C3H/HeN (C3H) and CBA/JN (CBA) all of identical AhR genotype. The BALB/cAnN strain had a more marked induction of a number of glutathione S‐transferase (GST) sub‐families, particularly the GSTmu gene family, compared with the other two strains. To assess the effects of GSTs induction to metabolize carcinogens, TCDD (40 µg kg^−1^) was administered to BALB and CBA strains, followed 24 h later by an i.p. injection of low or high dose of benzo[a]pyrene (B[a]P, 50 or 200 mg kg^−1^). The ^32^P‐postlabelling analysis showed that administration of TCDD alone failed to induce DNA adduct formation in both BALB and CBA strain mouse livers. The low dose of B[a]P alone produced DNA adduct in the liver of both strains to a similar extent. Treatment with TCDD 24 h before the low dose of B[a]P suppressed the formation of B[a]P‐induced DNA‐adduct more markedly in the BALB strain compared with the CBA strain. Taken together, these findings show that TCDD treatment causes strain‐specific alterations in gene expression and B[a]P‐induced DNA adduct formation in the liver of female mice of the same AhR^b2^ genotype. Furthermore, it suggests that TCDD‐treated female mice of the BALB strain may have genes whose products modify the toxicity of B[a]P as evidenced by TCDD‐induced alterations in B[a]P‐DNA adduct formation. Copyright © 2008 John Wiley & Sons, Ltd.