Ammenheuser M M, Berenson A B, Babiak A E, Singleton C R, Whorton E B
Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, USA.
Mutat Res. 1998 Jul 17;403(1-2):55-64. doi: 10.1016/s0027-5107(98)00027-x.
Reports of increases in the prevalence of marijuana smoking, especially among young people, have led to concerns about possible genotoxic effects from marijuana use due to exposure to the mutagenic and carcinogenic agents present in marijuana smoke. Prior studies of the adverse health consequences of marijuana smoking, using disease outcomes, have sometimes been confounded by the fact that most marijuana smokers also smoke tobacco. In the present study, the potential mutagenic effects of marijuana smoking were investigated with a somatic cell mutation assay that detects mutations occurring in vivo in the hprt gene. Subjects were volunteers recruited from a prenatal clinic that performs urine drug screens on all consenting patients. Blood samples were collected from 17 subjects whose drug screens indicated marijuana use, but who did not smoke tobacco or use cocaine or opiates, and 17 non-smokers with negative drug screens. Absence of tobacco use was confirmed by plasma cotinine tests. Cord blood samples were collected from newborns of 5 of the marijuana smokers and 5 non-smokers. Lymphocytes were isolated, cryopreserved, and later thawed and assayed with the autoradiographic hprt assay. The frequency of variant (mutant) lymphocytes (Vf) in the 17 non-smokers (+/- standard error) was 1.93 (+/- 0.17) per million evaluatable cells. The Vf of 17 marijuana smokers was more than three-fold higher, 6.48 (+/- 0.48) x 10(-6), a significant difference, p < 0.001. Cord blood lymphocytes from 5 newborns of non-smokers had a Vf of 0.85 (+/- 0.23) x 10(-6), compared to 2.55 (+/- 0.60) x 10(-6) for 5 newborns of marijuana smokers, significantly higher, p < 0.05. Because of the known association between increases in somatic mutations and the development of malignancies, this study indicates that marijuana smokers may have an elevated risk of cancer. For pregnant marijuana smokers, there is also concern for the possibility of genotoxic effects on the fetus, resulting in heightened risk of birth defects or childhood cancer.
有报告称大麻吸食率有所上升，尤其是在年轻人当中，这引发了人们对大麻使用可能产生的遗传毒性影响的担忧，因为大麻烟雾中存在诱变剂和致癌剂。此前关于大麻吸食对健康的不良后果的研究，以疾病结果为依据，有时会因大多数大麻吸食者也吸烟这一事实而受到混淆。在本研究中，通过一种体细胞突变试验来研究大麻吸食的潜在诱变作用，该试验可检测次黄嘌呤-鸟嘌呤磷酸核糖转移酶（hprt）基因在体内发生的突变。研究对象是从一家产前诊所招募的志愿者，该诊所会对所有同意的患者进行尿液药物筛查。采集了17名药物筛查显示吸食大麻但不吸烟、不使用可卡因或鸦片制剂的受试者以及17名药物筛查呈阴性的非吸烟者的血样。通过血浆可替宁检测确认未吸烟。从5名大麻吸食者和5名非吸烟者的新生儿中采集了脐带血样本。分离出淋巴细胞，进行冷冻保存，之后解冻并用放射自显影hprt试验进行检测。17名非吸烟者中变异（突变）淋巴细胞的频率（±标准误差）为每百万可评估细胞1.93（±0.17）。17名大麻吸食者的变异淋巴细胞频率高出三倍多，为6.48（±0.48）×10⁻⁶，差异显著，p<0.001。5名非吸烟者新生儿的脐带血淋巴细胞变异淋巴细胞频率为0.85（±0.23）×10⁻⁶，而5名大麻吸食者新生儿的该频率为2.55（±0.60）×10⁻⁶，显著更高，p<0.05。由于已知体细胞突变增加与恶性肿瘤发生之间存在关联，本研究表明大麻吸食者患癌症的风险可能会升高。对于怀孕的大麻吸食者，还存在对胎儿产生遗传毒性影响的可能性的担忧，这会导致出生缺陷或儿童癌症的风险增加。
