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.
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 GSTmicro gene family, compared with the other two strains. To assess the effects of GSTs induction to metabolize carcinogens, TCDD (40 microg 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 32P-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 AhRb2 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.
Wu
Qing
Q
School of Public Health, Fudan University, 130 Dongan Road, Shanghai 200032, China.
Suzuki
Junko S
JS
Zaha
Hiroko
H
Lin
Tien-Min
TM
Peterson
Richard E
RE
Tohyama
Chiharu
C
Ohsako
Seiichiroh
S
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D018736:DNA Adducts / Q000187:drug effects*; D017931:DNA Primers; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005838:Genotype; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D020411:Oligonucleotide Array Sequence Analysis; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity
D018736:DNA Adducts; D017931:DNA Primers; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D001564:Benzo(a)pyrene