Sbrana I, Lascialfari D, Rossi A M, Loprieno N, Bianchi M, Tortoreto M, Pantarotto C
Chem Biol Interact. 1983 Aug 1;45(3):349-57. doi: 10.1016/0009-2797(83)90081-9.
Styrene's capacity to induce chromosomal aberrations was studied in bone marrow cells of CD1 male mice. No mutagenic effect could be detected after either a 4-day treatment course with daily oral doses of 500 mg/kg or a 70-day course with daily oral doses of 200 mg/kg. Urinary elimination of styrene metabolites related to styrene-7,8-oxide formation (i.e. phenylethylene glycol, mandelic acid, benzoic acid, phenylglyoxylic acid and total mercapturic acids) was quantitatively evaluated in the group of mice given the 200 mg/kg dose. In parallel, kinetic studies were made on styrene and styrene-7,8-oxide blood concentrations in the same group of animals. These determinations were carried out on days 1 and 70 of treatment by spectrophotometric, gas chromatographic and mass fragmentographic procedures. Not even nanograms of styrene-7,8-oxide were found in the blood of styrene-treated mice. This suggests that the metabolite does not migrate from the cellular compartment where it is formed being immediately metabolized or irreversibly bound to cellular structures. This observation could well explain the lack of mutagenic effects observed.
在CD1雄性小鼠的骨髓细胞中研究了苯乙烯诱导染色体畸变的能力。在每日口服剂量为500mg/kg的4天治疗疗程或每日口服剂量为200mg/kg的70天疗程后，均未检测到诱变作用。在给予200mg/kg剂量的小鼠组中，对与苯乙烯-7,8-氧化物形成相关的苯乙烯代谢物（即苯乙二醇、扁桃酸、苯甲酸、苯乙醛酸和总巯基尿酸）的尿排泄进行了定量评估。同时，对同一组动物的苯乙烯和苯乙烯-7,8-氧化物血药浓度进行了动力学研究。这些测定在治疗的第1天和第70天通过分光光度法、气相色谱法和质谱碎片分析法进行。在经苯乙烯处理的小鼠血液中甚至未发现纳克级的苯乙烯-7,8-氧化物。这表明该代谢物不会从其形成的细胞区室迁移，而是立即被代谢或不可逆地结合到细胞结构上。这一观察结果很好地解释了所观察到的诱变作用的缺乏。
