Kanduc D, Ghoshal A, Quagliariello E, Farber E
Department of Pathology, University of Toronto, Ontario, Canada.
Biochem Biophys Res Commun. 1988 Jan 29;150(2):739-44. doi: 10.1016/0006-291x(88)90453-6.
DNA from hepatocyte nodules induced in rats with dietary DL-ethionine and from the surrounding non-nodular liver contained less 5-methyldeoxycytidine per deoxycytidine when compared with that from normal adult liver. The degree of apparent hypomethylation, 37% in nodules and 20% in the surrounding liver, decreased somewhat (29% and 16% respectively) at 2 weeks after terminating the exposure to ethionine. Nodules and surrounding liver, like normal liver, responded to partial hepatectomy with a decrease in the 5-methyldeoxycytidine level at 24 hrs and a return to the level at the time of partial hepatectomy by 38 hrs. These findings indicate the need for careful control of cell proliferation in comparing the levels of a post-replicative DNA modification, methylation, in proliferating and non-proliferating cell populations. These findings also suggest that a portion of the hypomethylation in preneoplastic nodules may be due to a bona fide decrease in the level of cytosine methylation in the parental strand of DNA. This hypomethylation could be one basis for the altered gene expression in hepatocyte nodules, possible precursors for liver cancer.
与正常成年肝脏的DNA相比，用膳食DL-乙硫氨酸诱导大鼠产生的肝细胞结节及其周围非结节性肝脏的DNA中，每摩尔脱氧胞苷所含的5-甲基脱氧胞苷较少。表观低甲基化程度在结节中为37%，在周围肝脏中为20%，在终止乙硫氨酸暴露2周后有所降低（分别为29%和16%）。结节和周围肝脏与正常肝脏一样，在部分肝切除术后24小时5-甲基脱氧胞苷水平降低，并在38小时恢复到部分肝切除时的水平。这些发现表明，在比较增殖和非增殖细胞群体中复制后DNA修饰（甲基化）水平时，需要仔细控制细胞增殖。这些发现还表明，癌前结节中的部分低甲基化可能是由于DNA亲本链中胞嘧啶甲基化水平的真正降低。这种低甲基化可能是肝细胞结节中基因表达改变的一个原因，而肝细胞结节可能是肝癌的前体。
