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Low oxygen tension, as found in tissues in vivo, alters the mutagenic activity of aristolochic acid I and II in primary fibroblast‐like rat cells in vitro
Author(s) -
Maier Peter,
Schawalder Hanspeter,
Weibel Beatrice
Publication year - 1987
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.2850100306
Subject(s) - in vivo , oxygen tension , in vitro , biology , aristolochic acid , biochemistry , biophysics , oxygen , chemistry , genetics , organic chemistry
The mutagenic activities of aristolochic acid I (AAI) and II (AAII), the two main components of aristolochic acid (AA), were tested for mutagenicity in vivo in a subcutaneous granulation tissue in rats and in vitro in the corresponding freshly isolated and cultured target cells. In vivo at equimolar dose, AAI induced 16 times more 6‐thioguanine resistant cells than AAII. Oxygen tension in vitro was adjusted to that found in vivo: in the subcutaneous connective tissue, the pO 2 was determined to be 40 ± 9 mm Hg, which corresponds in vitro to an O 2 concentration of 5% in the incubator atmosphere. In vitro, AAI was 19 times more mutagenic than AAII at this low oxygen tension but exhibited only 4 times greater activity than AAII under standard culture conditions. These results indicate that the genotoxic activity of AA in mammals is mainly caused by AAI and that the exposure of cells to AAI and AAII in vitro at low pO 2 corresponds more closely to the metabolic situation in vivo. Therefore, the mutagenic potency of the two chemicals can only be estimated correctly at tissue oxygen tension. The influence of pO 2 on the mutation frequencies seems to arise from a modulation of the activation/detoxification pathways.