Xilin Li, Yuan Le, Ji-Eun Seo, Xiaoqing Guo, Yuxi Li, Si Chen, Roberta A Mittelstaedt, Nyosha Moore, Sharon Guerrero, Audrey Sims, Sruthi T King, Aisar H Atrakchi, Timothy J McGovern, Karen L Davis-Bruno, David A Keire, Rosalie K Elespuru, Robert H Heflich, Nan Mei
Propranolol is a widely used β-blocker that can generate a nitrosated derivative, N-nitroso propranolol (NNP). NNP has been reported to be negative in the bacterial reverse mutation test (the Ames test) but genotoxic in other in vitro assays. In the current study, we systematically examined the in vitro mutagenicity and genotoxicity of NNP using several modifications of the Ames test known to affect the mutagenicity of nitrosamines, as well as a battery of genotoxicity tests using human cells. We found that NNP induced concentration-dependent mutations in the Ames test, both in two tester strains that detect base pair substitutions, TA1535 and TA100, as well as in the TA98 frameshift-detector strain...
May 18, 2023: Regulatory Toxicology and Pharmacology: RTP