Chen Y K, Lin L M, Hsue S S, Lin D T
Oral Pathology Department, School of Dentistry, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, Taiwan.
Oral Oncol. 2002 Feb;38(2):158-62. doi: 10.1016/s1368-8375(01)00039-2.
Placental glutathione S-transferase (GST-P) may facilitate cell proliferation and inhibit apoptosis, hence allowing for the expansion of a population of initiated tumor cells. The enhanced expression of GST-P at the protein level has been reported previously in chemically induced oral carcinomas in hamster buccal-pouch mucosa but the expression of GST-P at the mRNA level has not yet been demonstrated. The purpose of the present study was to assess the GST-P mRNA expression in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal-pouch carcinomas using a reverse transcription-polymerase chain reaction (RT-PCR). Thirty-five outbred, young (6 weeks old), male, Syrian golden hamsters (Mesocricatus auratus) were randomly divided into one experimental group (15 animals), and two control groups (10 animals each). Bilateral pouches of a group of 15 animals of the experimental group were painted with a 0.5% DMBA solution three times a week for 12 weeks while each animal of one of the control groups was similarly treated with mineral oil. Another control group of 10 animals was untreated throughout the experiment. Areas of dysplasia and squamous-cell carcinomas with a 100% tumor incidence developed in all of the DMBA-treated buccal pouches. The mineral oil-treated and untreated pouches revealed no obvious changes. Placental glutathione S-transferase mRNA was demonstrated to be present amongst all the 12-week DMBA-treated hamster buccal-pouch mucosa animals, but not for the untreated animals or the animals for which the buccal pouch was treated with mineral oil. Multiple potential regulatory pathways including gene amplification, enhanced mRNA stability, chromosomal translocation/gene rearrangement, and hypomethylation of the promoter region can contribute to the overexpression of GST-P mRNA in DMBA-induced hamster buccal-pouch carcinomas. Further study is necessary to completely understand which candidate mechanism(s) will contribute principally to the increased GST-P mRNA expression in oral experimental carcinogenesis.
胎盘型谷胱甘肽S-转移酶（GST-P）可能促进细胞增殖并抑制细胞凋亡，从而使一群起始肿瘤细胞得以扩增。先前已有报道称，在仓鼠颊囊黏膜化学诱导的口腔癌中，GST-P蛋白水平表达增强，但GST-P mRNA水平的表达尚未得到证实。本研究的目的是使用逆转录-聚合酶链反应（RT-PCR）评估7,12-二甲基苯并[a]蒽（DMBA）诱导的仓鼠颊囊癌中GST-P mRNA的表达。35只远交、年轻（6周龄）、雄性叙利亚金仓鼠（Mesocricatus auratus）被随机分为一个实验组（15只动物）和两个对照组（每组10只动物）。实验组的15只动物双侧颊囊每周用0.5% DMBA溶液涂抹3次，持续12周，而其中一个对照组的每只动物用矿物油进行类似处理。另一个由10只动物组成的对照组在整个实验过程中未接受任何处理。所有经DMBA处理的颊囊中均出现了发育异常区域和鳞状细胞癌，肿瘤发生率为100%。经矿物油处理和未处理的颊囊未出现明显变化。结果表明，在所有经12周DMBA处理的仓鼠颊囊黏膜动物中均检测到胎盘型谷胱甘肽S-转移酶mRNA，但未处理动物或颊囊用矿物油处理的动物中未检测到。包括基因扩增、mRNA稳定性增强、染色体易位/基因重排以及启动子区域低甲基化在内的多种潜在调控途径，可能导致DMBA诱导的仓鼠颊囊癌中GST-P mRNA的过表达。有必要进行进一步研究，以全面了解在口腔实验性致癌过程中，哪种候选机制将主要导致GST-P mRNA表达增加。
