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Clone 8 Cells by Aflatoxin B1 and Four Other Furocoumarins Isolated from Two Nigerian Medicinal Plants
University of Southern California Cancer Research Laboratories, Los Angeles, California 90033
Mutation by aflatoxin B1 (AFB1), imperatorin, marmesin, chalepin, and 8-methoxypsoralen (MOP), with and without black light (BL; long-wavelength ultraviolet light) activation, was determined at the hypoxanthine-guanine phosphoribosyltransferase locus (8-azaguanine resistance) in Chinese hamster V79 cells and at the ouabain locus in mouse C3H/10T
cells. Transformation by these furocoumarins under the same activation conditions was also investigated in C3H/10T
cells. In V79 cells, AFB1 induced a 4-fold maximum mutation frequency over controls under BL activation at a concentration of 5 µg/ml; marmesin induced a 2-fold increased mutation frequency at 1.5 µg/ml; MOP induced a 19-fold increase at 10 µg/ml; chalepin induced a 3-fold increase at 5 µg/ml; and imperatorin induced a 20-fold increase at 10 µg/ml. Essentially no mutation was observed at the ouabain-resistant (Ouar) locus in C3H/10T
cells with any of these compounds. In the transformation assays, type II and type III foci were observed at a 1-µg/ml addition of AFB1 with or without BL activation; while with MOP and imperatorin, these types of foci were observed only with BL activation. Marmesin, although relatively more cytotoxic than the other furocoumarins studied, with a 50% lethal dose of less than 0.5 µg/ml, was not as mutagenic or potentially carcinogenic as were AFB1, imperatorin, or MOP with BL activation. These furocoumarins are considered to be involved in the etiology of the high incidence of skin cancer in Nigeria. Our experiments reinforce that concept and suggest that exposure to these furocoumarins may constitute a real carcinogenic hazard.
1 Fellow of the International Agency for Research on Cancer, Lyon, France. Present address: Department of Biochemistry, University of Ibadan, Ibadan, Nigeria.
2 Supported by a Fellowship from Training Grant 1-T32-CA-09320 from the National Cancer Institute, NIH.
3 To whom requests for reprints should be addressed.
Received 7/ 2/82. Accepted 11/23/82.
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