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Proceedings of the National Academy of Sciences, Vol 91, 3147-3150, Copyright © 1994 by National Academy of Sciences
Y Zhang, TW Kensler, C Cho, GH Posner and P Talalay
Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)butane] was recently
isolated from one variety of broccoli as the major and very potent inducer
of phase 2 detoxication enzymes in murine hepatoma cells in culture. Since
phase 2 enzyme induction is often associated with reduced susceptibility of
animals and their cells to the toxic and neoplastic effects of carcinogens
and other electrophiles, it was important to establish whether sulforaphane
could block chemical carcinogenesis. In this paper we report that
sulforaphane and three synthetic analogues, designed as potent phase 2
enzyme inducers, block the formation of mammary tumors in Sprague-Dawley
rats treated with single doses of 9,10-dimethyl-1,2-benzanthracene. The
analogues are exo-2-acetyl-exo-6-isothiocyanatonorbornane,
endo-2-acetyl-exo-6-isothiocyanatonorbornane, and
exo-2-acetyl-exo-5-isothiocyanatonorbornane. When sulforaphane and
exo-2-acetyl-exo-6-isothiocyanatonorbornane were administered by gavage (75
or 150 µmol per day for 5 days) around the time of exposure to the
carcinogen, the incidence, multiplicity, and weight of mammary tumors were
significantly reduced, and their development was delayed. The analogues
endo-2-acetyl-exo-6-isothiocyanatonorbornane and
exo-2-acetyl-exo-5-isothiocyana-tonorbornane were less potent protectors.
Thus, a class of functionalized isothiocyanates with anticarcinogenic
properties has been identified. These results validate the thesis that
inducers of phase 2 enzymes in cultured cells are likely to protect against
carcinogenesis.
ARTICLE
Anticarcinogenic Activities of Sulforaphane and Structurally Related Synthetic Norbornyl Isothiocyanates
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|
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|
|
|
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|
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|
|
 |
|
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|
|
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