Stewart B W, Ward E J
Childrens Leukaemia and Cancer Research Unit, Prince of Wales Childrens Hospital, Randwick, NSW, Australia.
IARC Sci Publ. 1987(84):64-7.
Different levels of damage and repair to eu- and heterochromatic DNA from the livers of rats receiving a dose of 10 mg/kg N-nitrosodimethylamine (NDMA) were apparent. Preincorporated 3H-thymidine was lost rapidly from euchromatic DNA but persisted in the heterochromatic fraction. Persistent damage, determined as single-stranded regions binding to benzoylated DEAE-cellulose (BD-cellulose), was evident in heterochromatic DNA for up to three months. By subjecting rats treated with NDMA to partial hepatectomy, generation of single-stranded regions in the newly synthesized heterochromatic DNA could be demonstrated. Such structural defects were evident when hepatectomy was performed two months after administration of the carcinogen. These findings indicate that structural damage to nontranscribed DNA is one of the most persistent molecular lesions following exposure to nitrosamines.
接受10mg/kg剂量N-亚硝基二甲胺（NDMA）的大鼠肝脏中，常染色质和异染色质DNA的损伤及修复程度各异。预先掺入的3H-胸腺嘧啶迅速从常染色质DNA中丢失，但在异染色质部分持续存在。通过与苯甲酰化二乙氨基乙基纤维素（BD-纤维素）结合确定的持续性损伤，在异染色质DNA中长达三个月都很明显。对接受NDMA处理的大鼠进行部分肝切除后，可证明新合成的异染色质DNA中产生了单链区域。在给予致癌物两个月后进行肝切除时，这种结构缺陷很明显。这些发现表明，非转录DNA的结构损伤是接触亚硝胺后最持久的分子损伤之一。
