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癌症治疗对配子和胚胎的遗传及致畸作用。

Genetic and teratogenic effects of cancer treatments on gametes and embryos.

作者信息

Arnon J, Meirow D, Lewis-Roness H, Ornoy A

机构信息

Israel Ministry of Health and Laboratory of Teratology, Hebrew University Hadassah Medical School, Jerusalem.

出版信息

Hum Reprod Update. 2001 Jul-Aug;7(4):394-403. doi: 10.1093/humupd/7.4.394.

Abstract

Male and female germ cells vary in their sensitivity to the mutagenic effects of chemotherapy and radiotherapy, depending on their stage of maturation and the agent used. Although sperm DNA damage exists following treatment, no increase in genetic defects or congenital malformations was detected among children conceived to parents who have previously undergone chemotherapy or radiotherapy. The use of assisted reproductive technologies and micromanipulation techniques might increase this risk; hence caution should be exercised. In female cancer patients, miscarriage and congenital malformations are not increased following chemotherapy. However, when IVF and embryo cryopreservation is practised between or shortly after treatment, possible genetic risks to the growing oocytes exist, and hence the babies should be screened. During pregnancy, the potential teratogenic effects of chemotherapy influence the choice and timing of therapy. Termination is usually recommended in the first trimester. Second- and third-trimester exposure does not usually increase the teratogenic risk and cognitive development, but it may increase the risk of poor obstetric outcome and fetal myelosuppression. During the first two weeks after fertilization of the embryo, radiation is lethal but not teratogenic. High doses of radiation during pregnancy induce anomalies, impaired growth and mental retardation, and there may be an increased risk of childhood leukaemia and other tumours in the offspring.

摘要

男性和女性生殖细胞对化疗和放疗诱变作用的敏感性因其成熟阶段和所用药物而异。尽管治疗后存在精子DNA损伤,但在父母曾接受化疗或放疗后受孕的儿童中,未检测到遗传缺陷或先天性畸形增加。辅助生殖技术和显微操作技术的使用可能会增加这种风险,因此应谨慎行事。在女性癌症患者中,化疗后流产和先天性畸形并未增加。然而,在治疗期间或治疗后不久进行体外受精和胚胎冷冻保存时,正在生长的卵母细胞存在潜在的遗传风险,因此应对婴儿进行筛查。在怀孕期间,化疗的潜在致畸作用会影响治疗的选择和时机。通常建议在孕早期终止妊娠。孕中期和孕晚期接触通常不会增加致畸风险和认知发育风险,但可能会增加不良产科结局和胎儿骨髓抑制的风险。在胚胎受精后的头两周内,辐射是致命的,但不会致畸。怀孕期间高剂量辐射会诱发畸形、生长发育受损和智力迟钝,并且后代患儿童白血病和其他肿瘤的风险可能会增加。

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