Hepatocarcinogenic potency of mixed and pure enantiomers of trans-7,8-dihydrobenzo[a]pyrene-7,8-diol in trout.

Hepatocarcinogenic potency of mixed and pure enantiomers of trans-7,8-dihydrobenzo[a]pyrene-7,8-diol in trout.
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鳟鱼中反式 7,8-二氢苯并[a]芘-7,8-二醇的混合和纯对映体的肝癌效力。

DOI:
10.1016/0304-3835(93)90150-8
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发表时间:
1993
期刊:
影响因子:
9.7
通讯作者:
Williams,DE
Williams,DE
中科院分区:
医学1区
文献类型:
--
作者:
Kelly,JD;Dutchuk,M;Hendricks,JD;Williams,DE

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以虹鳟鱼胚胎和鱼苗为实验材料,研究了反式-7,8-二氢苯并[a]芘-7,8-二醇的致癌活性。用(±)-反式-7,8-二氢苯并[a]芘-7,8-二醇((±)BP-7,8-DHD)显微注射的胚胎在孵化后9个月发生肝肿瘤。然而,这种暴露方案导致了高死亡率。用0.01 - 1.0 μg(±)BP-7,8-DHD显微注射新孵化的囊鱼苗,产生与剂量有关的肝肿瘤(0 - 13%),与胚胎的结果相似,但没有高死亡率的问题。共注射囊鱼苗与(±)BP-7,8-DHD和β-萘啶酮或四氯化碳显著增强肿瘤反应(约100%)。3倍)。通过将0.5 - 5.0 μg剂量的BP-7,8-DHD的纯(+)和(−)对映体显微注射到囊内,评价了其相对致癌效力。结果表明,(−)对映体的效力是(+)的4 - 18倍。混合癌是观察到的最常见的肝脏肿瘤。这些结果表明,鳟鱼胚胎和囊鱼苗都响应于注射BP-7,8-DHD引发肝癌。与β-萘甲酮或四氯化碳共注射所观察到的显著增强表明,细胞色素P-450依赖性和脂质过氧化依赖性途径都可能参与该化合物的生物活化,推测是通过9,10-位的环氧化。与哺乳动物的情况一样,BP-7,8-DHD的(−)对映体是比(+)对映体更强的致癌物。
The hepatocarcinogenic potency of pure and racemic trans-7,8-dihydrobenzo[a]pyrene-7,8-diol was investigated in embryos and sac-fry rainbow trout. Embryos microinjected with (±)-trans-7,8-dihydrobenzo[a]pyrene-7,8-diol ((±) BP-7,8-DHD) developed liver tumors 9 months after hatching. However, this exposure protocol resulted in high mortalities. Microinjection of newly hatched sac-fry with 0.01 – 1.0 μg of (±) BP-7,8-DHD resulted in a dose-dependent production of liver tumors (0 – 13%) similar to the results with embryos but without the problem of high mortalities. Co-injection of sac-fry with (±) BP-7,8-DHD and either β-naphthoflavone or carbon tetrachloride significantly enhanced the tumor response (approx. 3-fold). The relative carcinogenic potencies of the pure (+) and (−) enantiomers of BP-7,8-DHD were evaluated by microinjection into sac-fry at doses of 0.5 – 5.0 μg. The results demonstrated that the (−) enantiomer was 4 – 18 times more potent than the (+). Mixed carcinomas were the most prevalent liver tumors observed. These results demonstrate that trout embryos and sac-fry are both responsive to hepatocarcinogenesis initiation by injection with BP-7,8-DHD. The marked enhancement seen with coinjection of sac-fry with β-naphthoflavone or carbon tetrachloride suggests that both cytochrome P-450-dependent and lipid peroxidation-dependent pathways could be involved in bioactivation of this compound, presumably through epoxidation at the 9,10-position. As is the case with mammals, the (−) enantiomer of BP-7,8-DHD is a more potent carcinogen than the (+) enantiomer.
DOI: 10.1016/0147-6513(88)90052-8
发表时间: 1988-12-01
影响因子: 6.8
作者:
HAWKINS, WE;WALKER, WW;LYTLE, JS
通讯作者: LYTLE, JS
膳食暴露和腹腔注射苯并[a]芘对虹鳟鱼的肝癌致癌性。
DOI: --
发表时间: 1985
期刊: Journal of the National Cancer Institute
影响因子: --
作者:
Hendricks,JD;Meyers,TR;Shelton,DW;Casteel,JL;Bailey,GS
通讯作者: Bailey,GS
由来自β-萘黄酮喂养的虹鳟鱼的细胞色素 P-450 的纯化同工酶催化的苯并[a]芘羟化酶。
DOI: 10.1016/0006-2952(84)90035-2
发表时间: 1984
影响因子: 5.8
作者:
Williams,DE;Buhler,DR
通讯作者: Buhler,DR
DOI: 10.1126/science.6304879
发表时间: 1983
期刊: Science (New York, N.Y.)
影响因子: --
作者:
Dix,TA;Marnett,LJ
通讯作者: Marnett,LJ
DOI: 10.1093/carcin/7.12.1957
发表时间: 1986-12-01
期刊: CARCINOGENESIS
影响因子: 4.7
作者:
ELING, T;CURTIS, J;MARNETT, LJ
通讯作者: MARNETT, LJ