Glatt H, Pauly K, Frank H, Seidel A, Oesch F, Harvey R G, Werle-Schneider G
Deutsches Institut für Ernährungsforschung, Potsdam-Rehbrücke, Germany.
Carcinogenesis. 1994 Nov;15(11):2605-11. doi: 10.1093/carcin/15.11.2605.
Six primary and 10 secondary benzylic alcohols derived from polycyclic aromatic hydrocarbons were tested for mutagenicity in Salmonella typhimurium TA98 in the presence of varying amounts of hepatic cytosol from adult male and female rats and 3'-phosphoadenosine-5'-phosphosulfate, the cofactor for sulfotransferases. With the exception of 1-(9-anthryl)ethanol, 4H-cyclopenta[def]-phenanthren-4-ol and 10-hydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene, all the benzylic alcohols were activated to mutagens. For 1-(1-pyrenyl)ethanol (1-HEP), 1-(2-pyrenyl)ethanol (2-HEP), 6-hydroxymethylanthanthrene (6-HMAA), 2-hydroxymethylpyrene (2-HMP), 10H-indeno[1,2,7,7a-bcd]pyren-10-ol (OH-IP), 3-hydroxy-3,4-dihydrocyclopenta[cd]pyrene (3-OH-H2-CPcdP) and 1-(6-benzo[a]pyrenyl)ethanol (6-HEBP), this is the first observation of a mutagenic activity. The primary alcohols 1-hydroxymethylpyrene, 2-HMP, 9-hydroxymethylanthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene and 6-hydroxymethylbenzo[a]pyrene, as well as the secondary alcohols 1-HEP and 3-OH-H2-CPcdP, were more efficiently activated by hepatic cytosol from females than by preparations from males (2.6- to 8-fold). A further compound, 6-HEBP showed significant, but relatively weak, effects in the presence of cytosol from females, whereas it was inactive in the presence of hepatic cytosol from males. The reverse sex difference was observed in the activation of 4H-cyclo-penta[def]chrysen-4-ol, the activity of cytosol from males amounting to about four times that from females. Four other compounds, 2-HEP, 7-hydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene, 6-HMAA and OH-IP, were activated with similar efficiency by hepatic cytosol from both sexes (< two-fold differences). The study indicates that different sulfotransferases are involved in the bioactivation of benzylic alcohols, including forms preferentially expressed in females as well as forms preferentially expressed in males, and that these enzymes qualitatively differ in their substrate tolerance for benzylic alcohols.
对源自多环芳烃的6种伯苄醇和10种仲苄醇进行了测试，以检测其在鼠伤寒沙门氏菌TA98中的致突变性，测试时存在来自成年雄性和雌性大鼠的不同量的肝细胞溶质以及硫酸转移酶的辅助因子3'-磷酸腺苷-5'-磷酸硫酸酯。除了1-(9-蒽基)乙醇、4H-环戊并[def]菲-4-醇和10-羟基-7,8,9,10-四氢苯并[a]芘外，所有苄醇都被激活成为致突变剂。对于1-(1-芘基)乙醇(1-HEP)、1-(2-芘基)乙醇(2-HEP)、6-羟甲基蒽并蒽(6-HMAA)、2-羟甲基芘(2-HMP)、10H-茚并[1,2,7,7a-bcd]芘-10-醇(OH-IP)、3-羟基-3,4-二氢环戊并[cd]芘(3-OH-H2-CPcdP)和1-(6-苯并[a]芘基)乙醇(6-HEBP)，这是首次观察到其致突变活性。伯醇1-羟甲基芘、2-HMP、9-羟甲基蒽、7-羟甲基-12-甲基苯并[a]蒽和6-羟甲基苯并[a]芘，以及仲醇1-HEP和3-OH-H2-CPcdP，被雌性大鼠的肝细胞溶质比被雄性大鼠的肝细胞溶质更有效地激活(2.6至8倍)。另一种化合物6-HEBP在雌性大鼠的肝细胞溶质存在下显示出显著但相对较弱的效应，而在雄性大鼠的肝细胞溶质存在下则无活性。在4H-环戊并[def] Chrysene-4-醇的激活中观察到相反的性别差异，雄性大鼠的肝细胞溶质活性约为雌性大鼠的四倍。其他四种化合物2-HEP、7-羟基-7,8,9,10-四氢苯并[a]芘、6-HMAA和OH-IP被两性的肝细胞溶质以相似的效率激活(差异小于两倍)。该研究表明，不同的硫酸转移酶参与了苄醇的生物活化，包括优先在雌性中表达的形式以及优先在雄性中表达的形式，并且这些酶在对苄醇的底物耐受性上存在质的差异。
