Jacobson-Kram D, Albertini R J, Branda R F, Falta M T, Iype P T, Kolodner K, Liou S H, McDiarmid M A, Morris M, Nicklas J A
Toxicology Group, Microbiological Associates, Rockville, MD 20850.
Environ Health Perspect. 1993 Oct;101 Suppl 3(Suppl 3):121-5. doi: 10.1289/ehp.93101s3121.
Using a multidisciplinary approach, we have measured various indicators of DNA damage in peripheral lymphocytes of human populations potentially at increased risk for cancer. Sister chromatid exchanges (SCE) and polycyclic aromatic hydrocarbon (PAH)-DNA adducts were evaluated in a group of firefighters; chromosomal aberrations and hprt mutations were evaluated in a group of cancer patients undergoing radioimmunoglobulin therapy (RIT); SCE and acrolein-modified DNA were measured in cancer chemotherapy patients and in pharmacists preparing chemotherapy prescriptions; and SCE and PAH-DNA adducts are being measured in U.S. army troops stationed in Kuwait. Our results indicate that both SCE and PAH-DNA adduct levels were not elevated in firefighters, but that other factors such as smoking status and race were risk factors for increased SCE and PAH-DNA adducts. RIT was found to increase background rates of chromosome-type aberrations and frequencies of hprt mutations and there was a strong correlation between levels of therapy-induced chromosome damage sustained in vivo and in vitro sensitivity to radiation-induced chromosome damage. Peripheral blood lymphocytes of cancer patients treated with cyclophosphamide showed higher levels of SCE and had a higher incidence of acrolein adducts in DNA. Lymphocytes from pharmacists preparing antineoplastic drugs were found to acquire increased in vitro sensitivity to SCE induction by phosphoramide mustard with increased lifetime duration of drug handling. A prospective, longitudinal study was performed to identify environmental factors that modulate genetic damage in breast cancer patients. Women with benign breast masses and no apparent disease served as controls. Mutant frequency, cloning efficiency, and chromosomal aberration frequency did not differ significantly among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)
我们采用多学科方法，测量了癌症潜在风险增加的人群外周淋巴细胞中各种DNA损伤指标。在一组消防员中评估了姐妹染色单体交换（SCE）和多环芳烃（PAH）-DNA加合物；在一组接受放射免疫球蛋白治疗（RIT）的癌症患者中评估了染色体畸变和次黄嘌呤磷酸核糖转移酶（hprt）突变；在癌症化疗患者和准备化疗处方的药剂师中测量了SCE和丙烯醛修饰的DNA；并且正在对驻扎在科威特的美国军队进行SCE和PAH-DNA加合物的测量。我们的结果表明，消防员的SCE和PAH-DNA加合物水平均未升高，但吸烟状况和种族等其他因素是SCE和PAH-DNA加合物增加的风险因素。发现RIT会增加染色体型畸变的背景率和hprt突变频率，并且体内治疗诱导的染色体损伤水平与体外对辐射诱导的染色体损伤的敏感性之间存在很强的相关性。接受环磷酰胺治疗的癌症患者外周血淋巴细胞显示出较高的SCE水平，并且DNA中丙烯醛加合物的发生率较高。发现准备抗肿瘤药物的药剂师的淋巴细胞随着药物处理寿命的延长，对磷酰胺芥诱导SCE的体外敏感性增加。进行了一项前瞻性纵向研究，以确定调节乳腺癌患者遗传损伤的环境因素。患有良性乳腺肿块且无明显疾病的女性作为对照。三组之间的突变频率、克隆效率和染色体畸变频率没有显著差异。（摘要截短为250字）
