tailieunhanh - Human Developmental Toxicants - Part 2

Chlorambucil là một tác nhân chống ung thư alkylating được sử dụng trị liệu trong việc quản lý của bệnh bạch cầu lymphocytic mãn tính, Hodgkin và u lympho không Hodgkin và một số khối u ác tính khác. Nó là một dẫn xuất của mechlorethamine, một độc tố phát triển con người. Như với alkylators khác, chlorambucil can thiệp với sao chép DNA và RNA sao chép-ankyl hóa và liên kết ngang sợi DNA (Lacy et al., 2004). Thuốc được thương mại có sẵn như là Leukeran ® và có một yếu tố nguy cơ mang thai của D. | Chlorambucil Chemical name 4- Bừ 2-chloroethyl amino benzene butanoic acid Alternate name Chloraminophene CAS 305-03-3 SMILES c1 ccc cc1 CCCC O O N CCCl CCCl HO Cl Cl INTRODUCTION Chlorambucil is an alkylating antineoplastic agent used therapeutically in the management of chronic lymphocytic leukemia Hodgkin s and non-Hodgkin s lymphoma and several other malignancies. It is a derivative of mechlorethamine another human developmental toxicant. As with other alkylators chlorambucil interferes with DNA replication and RNA transcription by alkylation and cross-linking DNA strands Lacy et al. 2004 . The drug is commercially available as Leukeran and has a pregnancy risk factor of D labeling states can cause fetal harm when administered to a pregnant woman it is probably teratogenic in humans . DEVELOPMENTAL TOXICOLOGY Animals The drug has been tested in the laboratory for developmental toxicity in rodents. As expected the drug is teratogenic in mice Didcock et al. 1956 and rats Murphy et al. 1958 when given intraperitoneally either once or twice during organogenesis at doses ranging from 6 to 40 mg kg day. Digit limb and central nervous system defects and cleft palate were produced. The drug is also embryolethal and causes stunting in rodents at doses in the range of 5 to 10 mg kg by the same route Murphy et al. 1958 Tanimura et al. 1965 . Humans Chlorambucil is also teratogenic in humans Four cases of congenital malformation were identified from published accounts in the literature as tabulated in Table 1. Doses administered resulting in 23 2007 by Taylor Francis Group LLC 24 Human Developmental Toxicants TABLE 1 Developmental Toxicity Profile of Chlorambucil in Humans Case Number Malformations Growth Retardation Death Functional Deficit Ref. 1 None 1 Revol et al. 1962 2 Kidney and ureter Shotton and Monie 1963 3 Eye 1 Rugh and Skaredoff 1965 4 None 1 Nicholson 1968 5 Kidney and ureter 1 Steeger and Caldwell 1980 6 Heart 1 Thompson and Conklin 1983 this toxicity ranged