Strauss V, Wiemer J, Leibold E, Kamp H, Walk T, Mellert W, Looser R, Prokoudine A, Fabian E, Krennrich G, Herold M, van Ravenzwaay B
BASF SE Experimental Toxicology and Ecology, Z 470, 67056 Ludwigshafen, Germany.
Toxicol Lett. 2009 Dec 1;191(1):88-95. doi: 10.1016/j.toxlet.2009.08.004. Epub 2009 Aug 14.
The impact of the strain on the metabolite profile of plasma samples in rats dosed with 2500 ppm 2-methyl-4-chlorophenoxyacetic acid (MCPA acid) or 45 mg/kg bw/day 4-chloro-3-nitroaniline (4C3N) for 4 weeks was evaluated. Four different strains were used: two Wistar strains (Crl:WI(Han), Han:RCC:WIST(SPF)), one Sprague-Dawley (Crl:CD) and one Fisher strain (F-344/Crl). The metabolite profiles in the plasma were measured by LC-MS and GC-MS. The profound changes of the metabolite values induced by the MCPA acid treatment outweighed slight deviations caused by physiological variations between the different rat strains. The metabolome changes of the MCPA acid in all strains could be related to toxicological "mode of action" patterns (peroxisome proliferator, renal organic anionic transporter inhibition) with Crl:WI(Han) rats as reference strain. 4C3N administration led to extravascular hemolytic anemia with a small number of metabolome changes, which were strain dependent. The metabolome pattern associated with "hemolytic anemia" established with the reference strain (Crl:Wi(Han)) was not sufficiently similar in other strains. Thus, comparable metabolome profiles were obtained in different rat strains for a compound inducing profound metabolite changes. For a compound with a weak profile the results were more variable and appeared to be strain dependent.
评估了2500 ppm 2-甲基-4-氯苯氧基乙酸（MCPA酸）或45 mg/kg体重/天4-氯-3-硝基苯胺（4C3N）给药4周对大鼠血浆样本代谢物谱的影响。使用了四种不同的品系：两种Wistar品系（Crl:WI(Han)，Han:RCC:WIST(SPF)），一种Sprague-Dawley品系（Crl:CD）和一种Fisher品系（F-344/Crl）。通过液相色谱-质谱联用（LC-MS）和气相色谱-质谱联用（GC-MS）测量血浆中的代谢物谱。MCPA酸处理引起的代谢物值的显著变化超过了不同大鼠品系之间生理差异导致的轻微偏差。以Crl:WI(Han)大鼠作为参考品系，所有品系中MCPA酸的代谢组变化都可能与毒理学“作用模式”（过氧化物酶体增殖剂、肾有机阴离子转运体抑制）相关。给予4C3N导致血管外溶血性贫血，代谢组变化较少，且具有品系依赖性。在其他品系中，与参考品系（Crl:Wi(Han)）建立的与“溶血性贫血”相关的代谢组模式并不足够相似。因此，对于一种诱导显著代谢物变化的化合物，在不同大鼠品系中获得了可比的代谢组谱。对于一种代谢组谱较弱变化的化合物，结果更具变异性，且似乎具有品系依赖性。
