Statistical treatment of cytotoxicity in Ames bacterial reverse mutation assays can provide additional structure–activity relationship information

Abstract

The bacterial reverse mutation assay, that is, the Ames test, measures mutations that reverse the inactivation of a gene involved in the synthesis of either histidine in Salmonella bacteria or tryptophan in Escherichia coli. The classic dose–response curve of an Ames assay plots number of reverse mutations (“revertants”) on the y-axis versus dose of the test chemical on the x-axis. Frequently, the dose–response curve resembles a parabola with a linear initial slope resulting from the accumulation of mutations, which transitions to a downward curvature resulting from cell killing (cytotoxicity) at increasingly higher doses of the test chemical. For regulatory purposes, a positive Ames test is usually considered as induction of twice the number of reverse mutations above background levels. For research purposes, the potency of the mutagenic response can be calculated from measuring the initial slope of the mutagenic response. This initial slope can be calculated in a manner that disentangles the downward pull on the initial slope value provided by the initiation of cytotoxicity. For a dose–response curve resembling a parabola, both the initial positive slope representing mutagenicity and the secondary negative slope representing cytotoxicity can be calculated from the same dose–response curve. The Ames test is the most commonly conducted genotoxicity assay. When a series of molecular congeners are assayed in the Ames test for mutagenicity, additional consideration of the cytotoxicity can provide important structure–activity relationship information.

In Silico Taste–Toxicity Study of New Hypothetical Hetero-Abiraterone Derivatives

“…Salmonella or Escherichia coli strains may be reversibly gene-mutated by chemicals that inactivate synthesis of histidine or tryptophan respectively. This bacterial mutation assay is DNA damage by base substitution and known as Ames test [36]. In this work, online prediction of Ames test showed that all Abiraterone products except A-T and A-P were genetically safe to the tested bacteria (Table 3.…”

Peroxynitrous Acid Generated In Situ from Acidified H2O2 and NaNO2. A Suitable Novel Antimicrobial Agent?

“…At higher concentrations, the test product led to a complete inactivation of the bacteria. As the complete inactivation can be a result of either antibacterial efficacy of the test product or a mutagenic effect, no clear result can be concluded on the mutagenic potential of the test product in this case [ 37 ].…”

In Silico Evaluation of the Physicochemical, Pharmacokinetics, and Toxicity Profiles of Sesquiterpene Lactones of South African Leaf (Vernonia amygdalina Delile)

“…Based on several studies, mutagenic substances may be carcinogenic. 33 Mutations are permanent changes in genes that may be responsible for many genetic disorders that result in certain cancers or syndromes. 34 Cancer is a disease characterized by malignant cells/tissues that grow quickly and uncontrollably and spread to other places in the patient's body.…”