2-aminofluorene-hepatic DNA adducts in congenic mouse lines differing in Ah responsiveness.

2-aminofluorene-hepatic DNA adducts in congenic mouse lines differing in Ah responsiveness.
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同源小鼠系中 2-氨基芴-肝 DNA 加合物的 Ah 反应性不同。

DOI:
10.1093/carcin/11.7.1233
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发表时间:
1990
期刊:
影响因子:
4.7
通讯作者:
Weber,WW
Weber,WW
中科院分区:
医学2区
文献类型:
--
作者:
Levy,GN;Weber,WW

文献摘要

被引文献

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用32 P核苷酸的HPLC分析方法,研究了β-萘酚酮(BNF)预处理对2-氨基芴(2-AF)-肝DNA加合物形成的影响。以C57 BL/6 J(B6)小鼠作为BNF-应答小鼠的例子,而B6(与B6同源的D-Ahda系)作为非应答系。BNF诱导Ah 136小鼠肝DNA加合物水平增加,但B6.D小鼠在60 mg/kg 2-AF腹腔注射后3 h,B6和B6.D的慢乙酰化对应物,即B6.A和B6.A. D-Nat 5Ahd(由B6.A和B6.D产生的新同源系),在诱导前加合物水平低于快速乙酰化。虽然B6.A和B6.A.D中的加合物水平在BNF诱导后增加,但加合物水平仍低于诱导的B6小鼠。在对BNF诱导反应的三个品系中,雄性小鼠的肝脏DNA加合物水平相对增加大于雌性小鼠。对于所有四条线,有或没有生物固氮预处理,更大的加合物水平被发现在女性。这些结果表明,芳香烃诱导的反应,以及快速乙酰化,可能是危险因素,在肝DNA损伤后芳胺曝光。雌性小鼠似乎比雄性小鼠更容易受到这种损害。
The influence of β-naphthoflavone (BNF) pretreatment on 2-aminofluorene (2-AF)-hepatic DNA adduct formation was evaluated inAh-responsive and non-responsive congenic mouse lines through use of HPLC analysis of32P nucleotides. C57BL/6J (B6) mice were used as an example of BNF-responsive mice while B6.D-Ahda line congenic with B6, was used as the non-responsive line. Induction at theAhlocus with BNF increased adduct levels in hepatic DNA in 136 mice but not in B6.D mice 3 h after a 60 mg/kg i.p. dose of 2-AF. The slow acetylator counterparts of B6 and B6.D, namely B6.A and B6.A.D-Nat5Ahd(a new congenic line produced from B6.A and B6.D), had lower adduct levels than the rapid acetylators before induction. Although adduct levels in B6.A and B6.A.D were increased following BNF induction, the level of adducts remained below those of induced B6 mice. In the three lines that responded to BNF induction, male mice had a greater relative increase in hepatic DNA adduct levels than females. For all four lines, with or without BNF pretreatment, greater adduct levels were found in the females. These results imply that responsiveness to aromatic hydrocarbon induction, as well as rapid acetylation, may be risk factors in hepatic DNA damage following arylamine exposure. Female mice appear to be more susceptible to such damage than males.