Hasan S S, Arshad M
School of Sciences, Indira Gandhi National Open University, New Delhi, India.
Q J Nucl Med. 1995 Dec;39(4):290-9.
The role of AMP and adenosine was investigated in the radiosensitization of normal brain tissues by chlorpromazine. Their metabolism was evaluated by estimating the levels of 5'-nucleotidase and adenosine deaminase activity in the brains of rats treated with chlorpromazine alone or chlorpromazine and irradiation. The extent of lipid peroxidation, measured in terms of the lipid peroxidase enzyme formed, increased with chlorpromazine treatment and irradiation. Chlorpromazine treatment was found to decrease AMP and adenosine metabolism, as shown by a marked reduction in the level of 5'-nucleotidase and ADA activity which was accompanied by a marked curtailment in the DNA, RNA and protein contents of the brain. Chlorpromazine was also found to increase the radiation-induced activity of acid phosphatase, indicating its action on the lysosomal activity of the brain cells. In the present study a low dose of chlorpromazine, i.e. 17 mg/kg body weight, was found to be more effective than a high dose of 34 mg/kg. The results of this study suggest that chlorpromazine probably sensitizes normal brain tissues to radiation by inhibiting AMP and adenosine metabolism via a hydroxy-radical induced decrease in DNA, RNA and protein metabolism with a concomitant increase in lysosomal activity.
研究了AMP和腺苷在氯丙嗪对正常脑组织放射增敏中的作用。通过评估单独用氯丙嗪或氯丙嗪与辐射处理的大鼠脑中5'-核苷酸酶水平和腺苷脱氨酶活性来评价它们的代谢。以形成的脂质过氧化物酶来衡量的脂质过氧化程度，随着氯丙嗪处理和辐射而增加。发现氯丙嗪处理会降低AMP和腺苷代谢，表现为5'-核苷酸酶水平和ADA活性显著降低，同时伴有脑DNA、RNA和蛋白质含量显著减少。还发现氯丙嗪会增加辐射诱导的酸性磷酸酶活性，表明其对脑细胞溶酶体活性的作用。在本研究中，发现低剂量氯丙嗪，即17mg/kg体重，比高剂量34mg/kg更有效。本研究结果表明，氯丙嗪可能通过抑制AMP和腺苷代谢，经由羟基自由基诱导的DNA、RNA和蛋白质代谢减少以及溶酶体活性的相应增加，使正常脑组织对辐射敏感。
