| In vitro: |
| Carcinogenesis,1990,11(8):1259–1263. | | Induction of cytochrome P450IA1 in rat colon and liver by indole-3-carbinol and 5,6-benzoflavone.[Reference: WebLink] | It is known that consumption of cruiciferous vegetables protects against the chemical induction of cancer in many organs. It has been suggested that this protection is mediated through an effect on the cytochrome P450 monooxygenase system. This system is responsible for the activation of a number of chemical carcinogens to their ultimate forms.
METHODS AND RESULTS:
In the present study, the effect of indole-3-carblnol (I3C) and 5,6-benzoflavone (5,6BF) on the expression of cytochrome P450IA1 in rat colon and liver has been investigated. Cytochrome P450IA1 mRNA was induced in colon following a single oral administration of I3C or 5,6BF. A biphasic induction profile was obtained with maxima at 4 and 16 h post-administration. Both Inducers caused an ∼2-fold increase in P450IA1 mRNA at 4 h and a 10-fold increase at 16 h. In contrast, both cytochrome P450IA1 and IA2 mRNAs were induced in liver, and the amount of P450IA mRNAs was increased over the control between 4 and 24 h. The total amount of P450IA mRNAs in liver at 4 and 16 h was increased about 2- and 4-fold respectively by I3C; 5,6BF induced the P450IA mRNAs 4- and 5-fold respectively. The expression of cytochrome P450IA1 and IA2 is induced by I3C and several flavones present in cruciferous vegetables.
CONCLUSIONS:
This suggests that one of the protective effects of cruciferous vegetables in the reduction of chemically induced cancer may be regulation of cytochrome P450s involved in the metabolism of the chemical carcinogens. | | Proceedings of the American Association for Cancer Research,1975,16(66):543. | | Effects of benzoflavones and trichloropropene oxide on aryl hydrocarbon hydroxylase activity and initiation of skin tumors.[Reference: WebLink] |
METHODS AND RESULTS:
7,8 Benzoflavone (7,8 BF) inhibited the initiation of skin tumors by 3 methylcholanthrene (MC) and 7,12 dimethylbenz(a) anthracene (DMBA). 5,6-Benzoflavone (5,6 BF) also inhibited tumor initiation by MC and DMBA but to a lesser degree.
Dose response studies of the capacity of 7,8 BF to inhibit tumor initiation by DMBA revealed that 7,8 BF was an effective inhibitor at concentrations equivalent to that of DMBA and a maximum inhibition was observed at 20 times that of DMBA. Epidermal aryl hydrocarbon dydroxylase was increased by 5,6 BF and inhibited by 7,8 BF when given either topically or i.p. When added in vitro 7,8 BF inhibited epidermal NADPH dependent covalent binding of tritiated MC to DNA by 50%. Trichloropropene oxide (TCPO) only slightly increased the in vitro covalent binding of MC to DNA in the above epidermal system. TCPO was effective in increasing the skin tumor initiating ability of MC, DMBA, BP and BP 4,5 epoxide. Mice that were topically treated with tritiated 7,8 BF, about 90% of the label in epidermal homogenates could be extracted into benzene 24 hours after treatment. 94% of the benzene extractable radioactivity was identified as 7,8 BF.
CONCLUSIONS:
The inhibition of skin tumor initiation by 7,8 BF appears to be partially related to its ability to inhibit the formation of electrophilic intermediate(s). |
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