Summary
The capacity of isolated mouse liver microsomes to alter the mutagenicity for bacteria of the primary carcinogen N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) and the secondary one dimethylni-trosamine (DMN) was studied. Microsomal activation of DMN and in-activation of MNNG were decreased by protein- and protein-choline-deficient diets and were increased by pretreatment with microsomal enzyme inducers. The decrease and increase paralleled the content of cytochrome P-450 present in the different microsomal preparations. With human liver microsomes of differing cytochrome P-450 contents similar correlation was obtained, whereas normal rat liver microsomes did not activate or inactivate DMN or MNNG. Oxidative de-methylation of DMN by mouse liver microsomes and the activation of DMN to a mutagen followed similar kinetics. Both reactions were inhibited by carbon monoxide and the inhibition was maximally reversed by monochromatic light at 450 nm. These observations indicate that at least some carcinogens are activated or inactivated by the unspecific cytochrome P-450 dependent enzyme system, suggesting that the extent of this biotransformation may be one factor influencing human carcinogenesis.
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Greim, H. et al. (1975). Cytochrome P-450 in the Activation and Inactivation of Carcinogens. In: Cooper, D.Y., Rosenthal, O., Snyder, R., Witmer, C. (eds) Cytochromes P-450 and b5 . Advances in Experimental Medicine and Biology, vol 58. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-9026-2_7
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DOI: https://doi.org/10.1007/978-1-4615-9026-2_7
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