Tumorigenicity of the optical enantiomers of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides in newborn mice: exceptional activity of (+)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.
Tumorigenicity of the optical enantiomers of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides in newborn mice: exceptional activity of (+)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.
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非对映体苯并[a]芘7,8-二醇-9,10-环氧化物的光学对映体在新生小鼠中的致瘤性：( )-7β,8α-二羟基-9α,10α-环氧-7,8的特殊活性，
DOI：
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发表时间：
1978
影响因子：
11.1
通讯作者：
A. Conney
中科院分区：
文献类型：
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作者：
M. Buening;P. Wislocki;W. Levin;H. Yagi;D. Thakker;H. Akagi;M. Koreeda*;D. Jerina;A. Conney
通过在小鼠出生后的第1、8和15天分别连续腹膜内注射1、2和4 nmol或2、4和8 nmol的每种化合物，测试苯并[a]芘和衍生自反式-7，8-二羟基-7，8-二氢苯并[a]芘的非对映体苯并[a]芘7，8-二醇-9，10-环氧化物的每种光学对映体的致瘤性。实验在动物34- 37周龄时终止。（+）-7 β，8 α-二羟基-9 α，10 α-环氧-7，8，9，10-四氢苯并[a]芘[（+）-BP-7 β，8 α-二醇-9 α，10 α-环氧化物2]具有特殊的致瘤性，而苯并[a]芘和苯并[a]芘7，8-二醇，9，10-环氧化物的其他三种光学纯异构体几乎没有或没有活性。这些结果证明了多环烃二醇环氧化物的光学活性异构体的致癌活性的差异。11%的对照小鼠患有肺肿瘤，而分别用总剂量为7或14 nmol的（+）-BP-7 β，8 α-二醇-9 α，10 α-环氧化物2治疗的小鼠中，71%和100%患有肺肿瘤。对照小鼠每只小鼠平均有0.12个肺肿瘤，而用总剂量为7或14 nmol的（+）-BP-7 β，8 α-二醇-9 α，10 α-环氧化物2处理的小鼠每只小鼠分别有1.72和7.67个肺肿瘤。用14 nmol（-）-BP-7 α，8 β-二醇-9 β，10 β-环氧化物2、（-）-BP-7 β，8 α-二醇-9 β，10 β-环氧化物1或（+）-BP-7 α，8 β-二醇-9 α，10 α-环氧化物1处理的小鼠每只动物分别有0.13、0.25和0.34个肺肿瘤。
The tumorigenicities of benzo[a]pyrene and each optical enantiomer of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides derived from trans-7,8-dihydroxy-7,8-dihydrobenzol[a]pyrene were tested by sequential intraperitoneal injection of mice with 1,2, and 4 nmol, or with 2, 4, and 8 nmol of each compound on the 1st, 8th, and 15th day of life, respectively. The experiment was terminated when the animals were 34--37 weeks old. (+)-7beta, 8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzol[a]pyrene [(+)-BP-7beta,8alpha-diol-9alpha,10alpha-epoxide 2] had exceptional tumorigenicity, whereas benzo[a]-pyrene and the other three optically pure isomers of the benzo[a]pyrene 7,8-diol,9,10-epoxides had little or no activity. These results demonstrate differences in the carcinogenic activities of optically active isomers of a polycyclic hydrocarbon diol epoxide. Eleven percent of control mice had pulmonary tumors, whereas 71% and 100% of the mice treated with a total dose of 7 or 14 nmol of (+)-BP-7beta,8alpha-diol-9alpha,10alpha-epoxide 2, respectively, had pulmonary tumors. Control mice had an average of 0.12 pulmonary tumors per mouse, whereas mice treated with a total dose of 7 or 14 nmol of (+)-BP-7beta,8alpha-diol-9alpha,10alpha-epoxide 2 had 1.72 and 7.67 pulmonary tumors per mouse, respectively. Mice treated with 14 nmol of (-)-BP-7alpha,8beta-diol-9beta,10beta-epoxide 2, (-)-BP-7beta,8alpha-diol-9beta,10beta-epoxide 1, or (+)-BP-7alpha,8beta-diol-9alpha,10alpha-epoxide 1 had 0.13, 0.25, and 0.34 pulmonary tumors per animal, respectively.