PMID: 6409603Jan 1, 1983Paper

Penetration of AF-2 and 4NQO into multicell spheroids

Environmental Mutagenesis
P L Olive, R E Durand

Abstract

The mutagenicity of 4NQO and AF-2 was evaluated in a multicell system, Chinese hamster V79 spheroids, in order to determine the effects of drug delivery and metabolism on toxicity and mutagenicity. Both 4NQO and AF-2 undergo metabolic reduction of the nitro group to produce toxic intermediates. However, 4NQO is metabolized under oxic as well as hypoxic conditions, while AF-2 is reduced predominantly under hypoxia. This difference is apparently responsible for the observed pattern of toxicity and mutagenicity towards cells of large spheroids. Fluorescence microscopy revealed that 4NQO fluorescence localizes primarily in external (oxic) cells while AF-2 can penetrate further into the hypoxic region of spheroids. Although 4NQO is a far more potent single cell mutagen than AF-2 for equimolar exposures of single cells, the internal cells of spheroids exposed to 7.5 micrograms/ml of either agent under hypoxia were more readily mutated by AF-2 than by 4NQO.

References

Apr 1, 1978·Chemico-biological Interactions·D R McCallaB Broughton
Jun 1, 1968·The British Journal of Radiology·A H Nias, M Fox
Jun 1, 1981·Chemico-biological Interactions·P L Olive
Feb 1, 1982·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·R E Durand, P L Olive
Mar 1, 1982·International Journal of Radiation Oncology, Biology, Physics·P L Olive
Nov 1, 1981·Cytometry·R E Durand
Nov 30, 1967·Biochemical and Biophysical Research Communications·M TadaT Takahashi

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Citations

Aug 1, 1984·International Journal of Radiation Oncology, Biology, Physics·P L Olive
Jun 10, 2010·Journal of Pharmaceutical Sciences·Nelita T Elliott, Fan Yuan
Jan 1, 1986·Environmental Mutagenesis·P L Olive
Oct 16, 2003·Journal of Agricultural and Food Chemistry·Mitsuo Miyazawa, Masayoshi Hisama
Dec 20, 1999·Journal of Agricultural and Food Chemistry·M MiyazawaH Kameoka

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