化疗所致老年弥漫大B细胞淋巴瘤患者细胞遗传学损伤的研究

Cytogenetic damage in elderly patients with diffuse large B-cell lymphoma caused by chemotherapy

目的探讨姐妹染色单体交换(sister chromatid exchanges, SCE)率、次黄嘌呤鸟嘌呤磷酸核糖转移酶(hypoxanthine guanine phosphoribosyl transferase, HPRT)基因突变率、微核(micronucleus, MN)率对老年弥漫大B细胞淋巴瘤患者化疗所致细胞遗传学损伤的评估及预测意义。方法检测87例老年弥漫大B细胞淋巴瘤患者4周期化疗前后外周血淋巴细胞SCE率、HPRT基因突变率、MN率以及白细胞(White blood cell, WBC)计数,比较各周期化疗前后SCE率、HPRT基因突变率、MN率的变化以及检验上述3项指标分别与化疗前、后WBC变化的相关性。结果 (1) 1～4周期各周期化疗后SCE率均较各周期化疗前增加,差异具有统计学意义(P<0.05);各周期化疗后的SCE率呈现升高趋势,差异具有统计学意义(P<0.05)。(2)每个周期化疗后的HPRT基因突变率均较化疗前增加,差异具有统计学意义(P<0.05); 1～4周期各周期化疗后的HPRT基因突变率升高差异无统计学意义(P>0.05)。(3)各周期化疗后的MN率均较治疗前增加,差异具有统计学意义(P<0.05);各周期化疗后的MN率呈现升高趋势,差异具有统计学意义(P<0.05)。(4) 1～4周期化疗后SCE率的升高程度、MN率的升高程度与WBC下降程度均呈负相关(P<0.001),HPRT基因突变率的升高程度与WBC计数下降程度呈正相关(P<0.001)。结论 SCE率、HPRT基因突变率、MN率能够很好地反映化疗所致细胞遗传学方面的损伤程度。SCE率、HPRT基因突变率、MN率与骨髓抑制程度具有相关性,可以作为预测因子,提示化疗导致的血液学毒性的严重程度。

Objective To evaluate the effect of SCE rate,HPRT gene mutation rate and MN rate as the indicator of cytogenetic damage induced by chemotherapy in elderly patients with diffuse large B-cell lymphoma.MethodsWe detected the changes of SCE rate,HPRT gene mutation rate and MN rate in peripheral blood lymphocytes of 87 elderly patients with diffuse large B-cell lymphoma before and after four-cycle chemotherapy and analysis the correlation between them with the changes of WBC before and after chemotherapy.ResultsThe SCE rate after each chemotherapy during the four cycles was increased significantly,compared with that before(P<0.05),and the elevated trend of the SCE rate during the four courses was significantly(P<0.05).The HPRT gene mutation rate after each cycle was increased too,compared with that before,the difference was statistically significant(P<0.05),but the increasing trend was not significant during the four cycles(P>0.05).The MN rate after each chemotherapy was increased significantly compared with that before(P<0.05),and the increasing trend was significant during the four cycles(P<0.05).The elevated trend of SCE rate and MN rate was negatively correlated with the decrease of WBC counts(P<0.001),and the HPRT gene mutation rate was positive correlated with WBC counts(P<0.001).ConclusionSCE rate,HPRT gene mutation rate and MN rate can reflect the degree of cytogenetic damage caused by chemotherapy.SCE rate,HPRT gene mutation rate and MN rate are correlated with the degree of bone marrow suppression,which can be used as predictors to indicate the severity of hematological toxicity caused by chemotherapy.