The proline form of p53 codon 72 polymorphism is associated with endometriosis

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Title:	The proline form of p53 codon 72 polymorphism is associated with endometriosis
Authors:	Chang, CC;Hsieh, YY;Tsai, FJ;Tsai, CH;Tsai, HD;Lin, CC
Contributors:	附設醫院兒科部;China Med Coll Hosp, Dept Pediat & Med Genet, Taichung, Taiwan;China Med Coll Hosp, Dept Pediat & Med Genet, Taichung, Taiwan;China Med Coll Hosp, Dept Family Med, Taichung, Taiwan;Li Shin Hosp, Dept Obstet & Gynecol, Taichung, Taiwan
Date:	2002
Issue Date:	2010-09-24 14:26:27 (UTC+8)
Publisher:	ELSEVIER SCIENCE INC
Abstract:	Neocarzinostatin is a potent antitumor antibiotic and is a prodrug, which induces genome damage after activation by a thiol. The prodrug is stored as a protein-bound chromophore that contains an enediyne nucleus. A thiolate attack on the chromophore cyclizes the nucleus and produces radicals that abstract hydrogen from DNA. Because thiol is the only cofactor in the vital activation process, the structure of the thiol plays an important role in the activity of the drug,. Here we systematically examine the effect of the electronic structure of some thiols on the efficiency of the drug, and compare particularly aromatic with aliphatic thiols. The values of drug-induced base release from DNA are remarkably different between thiophenol (3.6%) and benzyl mercaptan (12.5%), the activity of which is comparable with those of aliphatic thiols. Cleavage results determined by DNA electrophoresis are consistent with the results of base release; they show that the total number of DNA lesions is more than 3-fold lower for thiophenol than for aliphatic thiols or benzyl mercaptan. We conclude that among aromatic thiols, only those that have delocalized thiol sulfur electrons can substantially reduce the DNA cleavage activity. This result suggests that the effect of an aromatic ring arises from an inductive effect imposed on the thiol sulfur electron through pi-resonance rather than through effects such as aromatic stacking, steric hindrance, or hydrophobic interaction. Replacing thiophenol with substituted derivatives with electron-releasing or -withdrawing groups changes the drug activity and supports the important role of the electronic structure of the thiol sulfur in determining the drug activity.
Relation:	FERTILITY AND STERILITY 77(1):43-45
Appears in Collections:	[China Medical University Hospital] Jurnal articles

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