Lack Of Mutagenic Activity Research Articles

The impact of astaxanthin on radiation-induced chromosome aberrations in human peripheral blood lymphocytes in vitro

Aim. Research objective is to establish the possibility of modifying the astaxanthin (a carotenoid from a xanthophyll group) radiation-induced cytogenetic effects in human peripheral blood lymphocytes (PBLs) in vitro. Methods. The cultivation of PBLs from four conventionally healthy volunteers, the preparation and analysis of uniformly stained slides of metaphase chromosomes. Astaxanthin in final concentrations of 2, 10 and 20 µg/ml was added into the culture of PBL prior to the incubation before irradiation with γ-quanta in a dose of 1 Gy. Results. Astaxanthin did not affect the level and spectrum of chromosome damage in non-irradiated PBLs both in individual persons, and along the group on average (P>0.05), indicating a lack of mutagenic activity. The effect of astaxanthin at a concentration of 20 μg/ml on irradiated PBLs resulted in a significant reduction of radioinduced cytogenetic effect in all donors. Medium-group level of chromosome aberrations decreased almost 3 times and was characterized by statistically significant (P<0.001) decrease in frequency of chromosomal type aberrations due to the classical unstable cytogenetic markers of radiation effect, dicentrics and ring chromosomes. Conclusions. Astaxanthin at a concentration of 20 µg/ml was found to reduce the mutagenic effect of ionizing radiation, thus suggesting its powerful radioprotective potential. Keywords: astaxanthin, culture of human peripheral blood lymphocytes, radiation mutagenesis, chromosome aberrations, radioprotective effect.

Multi-walled carbon nanotubes: Lack of mutagenic activity in the bacterial reverse mutation assay

The mutagenic effect of multi-walled carbon nanotubes (MWCNTs) characterised by small surface/volume ratio, high diameter and less than 0.1% of metal contaminants was evaluated by the bacterial reverse mutation assay (Ames test) on Salmonella typhimurium TA 98 and TA 100 strains, and on Escherichia coli WP2 uvrA strain, in presence and in absence of the metabolic activation system S9. A preliminary cytotoxicity assay was carried out to ensure that cytotoxicity did not interfere with response. MWCNTs resulted devoid of mutagenic effect in the bacterial cellular systems tested in that they did not significantly increase the number of revertant colonies. The mutagenic activity did not even appear in presence of the metabolic activator, so we can exclude that MWCNTs metabolites, produced via cytochrome-based P450 metabolic oxidation system, may act as mutagens. Carbon nanomaterials seem to exhibit different biological activities and different toxicities in relation to their physico-chemical characteristics, size, shape, crystallinity and presence of metal traces, so it is difficult to establish their health risk. Due to the limited background of genotoxicity studies and the increased occupational and public exposure to nanomaterials, present results appear useful to extend the knowledge on the safety of carbon nanotubes in view of their possible applications.

Is estradiol a genotoxic mutagenic carcinogen?

The natural hormone 17 beta-estradiol (E2) induces tumors in various organs of rats, mice, and hamsters. In humans, slightly elevated circulating estrogen levels caused either by increased endogenous hormone production or by therapeutic doses of estrogen medications increase breast or uterine cancer risk. Several epigenetic mechanisms of tumor induction by this hormone have been proposed based on its lack of mutagenic activity in bacterial and mammalian cell test systems. More recent evidence supports a dual role of estrogen in carcinogenesis as a hormone stimulating cell proliferation and as a procarcinogen inducing genetic damage. Tumors may be initiated by metabolic conversion of E2 to 4-hydroxyestradiol catalyzed by a specific 4-hydroxylase (CYP1B1) and by further activation of this catechol to reactive semiquinone/quinone intermediates. Several types of direct and indirect free radical-mediated DNA damage are induced by E2, 4-hydroxyestradiol, or its corresponding quinone in cell-free systems, in cells in culture, and/or in vivo. E2 also induces various chromosomal and genetic lesions including aneuploidy, chromosomal aberrations, gene amplification, and microsatellite instability in cells in culture and/or in vivo and gene mutations in several cell test systems. These data suggest that E2 is a weak carcinogen and weak mutagen capable of inducing genetic lesions with low frequency. Tumors may develop by hormone receptor-mediated proliferation of such damaged cells.

Lack of mammalian mutagenicity of the potent bacterial mutagen tris(2,3-dibromopropyl)phosphate and its metabolite 2-bromoacrolein

The flame retardant tris(2,3-dibromopropyl)phosphate (Tris–BP) and its metabolite 2-bromoacrolein (2BA) are very potent bacterial mutagens in Salmonella typhimurium ( S. typhimurium) TA 100. In this study, we showed that 2BA and Tris–BP are also mutagenic in S. typhimurium TA 104, which detects mutations at AT base pairs, while TA 100 detects mutations at CG basepairs. We also studied the mutagenicity of 2BA in mammalian cells in vitro and in the rat in vivo. Firstly, 2BA was tested in the human lymphoblastoid cell line TK6. The results showed that there was no increase in mutation frequency at the hprt locus, whereas there was a large decrease in cell survival. Secondly, a shuttle vector system was used to study the induction of mutations by 2BA:DNA adducts. The vector was modified by insertion of a single-stranded oligonucleotide containing on average one 2BA:DNA adduct. No increase in mutation frequency above background was detected after replication of this vector in SV40 transformed normal human fibroblasts. Because the liver is a major site for bioactivation of Tris–BP to 2BA in vivo, we tested the initiating capacity of Tris–BP in the rat liver in a modified Solt&Farber initiation and promotion system. Administration of Tris–BP resulted in a small increase in the number of preneoplastic γ-glutamyl-transpeptidase positive (GGT +) foci in the liver compared to control animals (only significant in the lowest size class). Modification of the experimental protocol by performing partial hepatectomy 24 h after the administration of Tris–BP, did not increase the number of GGT + or glutathione S-transferase-P (GST-P +) positive foci above the control level. Taken together, these results indicate that, in spite of a high mutagenicity in S. typhimurium, 2BA and Tris–BP have low or negligible mutagenic effects in mammalian systems. The lack of mutagenic activity may explain why Tris–BP is not a carcinogen in the rat liver.

Thalidomide: lack of mutagenic activity across phyla and genetic endpoints

The human and rabbit teratogen thalidomide has been tested for mutagenicity in a wide range of assays, ranging from bacterial gene mutation assays conducted in vitro to in vivo cytogenetic assays conducted using rabbits, and including a variety of human-derived tissues. Thalidomide was not mutagenic to 6 strains of Salmonella when tested both in the presence and absence of Aroclor-induced rat liver S9 mix. This inactivity was confirmed in strains TA98 and TA100 using a 1-h pre-incubation assay protocol with the same S9 mix (10% S9), and additionally, in strain TA98 using 3 concentrations of S9 (4%, 10% and 30% S9 in S9 mix). Thalidomide was not clastogenic either to cultured human lymphocytes (whole blood cultures, minus S9 mix) or to Chinese hamster ovary (CHO) cells treated in vitro. Further, no cytotoxicity was observed in purified human lymphocytes when exposed to thalidomide up to the limit of its solubility in the medium in the presence and absence of liver S9 from Aroclor-induced pregnant rabbit. The CHO assays were conducted without metabolic activation and in the presence of a variety of sources of auxiliary metabolic activation (PB/ βNP-induced rat liver S9 mix, pooled male and female human liver S9 mix, uninduced and Aroclor-induced pregnant rabbit liver S9 mix and foetal rabbit S9 mix). Thalidomide did not induce micronuclei in isolated human lymphocytes (minus S9 mix) and it was non-mutagenic to mouse lymphoma L5178Y TK +/− cells when tested to the limits of its solubility in the culture medium (±S9 mix). No indication of recombinogenic or clastogenic activity was observed for thalidomide when tested in Drosophila. In addition, it failed to induce chromosome aberrations in grasshopper neuroblasts when tested in the presence and absence of Aroclor-induced rat liver S9 mix. Some unusual chromosome morphologies were observed in the grasshopper cytogenetic preparations indicating a potential of thalidomide to interact with chromosomal proteins. However, this potential was not evident in the human lymphocyte micronucleus assay, and thalidomide was apparently not reactive to the proteins of the mouse skin, as it gave negative results in a mouse local lymph node assay for skin sensitizing agents. Thalidomide was inactive in bone marrow micronucleus assays conducted using males and females from two strains of mice, and female New Zealand white rabbits. It is concluded that thalidomide is neither a mutagen nor an aneugen. This conclusion is discussed within the context of the results of earlier mutagenicity studies, the recent claim that thalidomide may be a heritable germ cell mutagen to humans, and the current interest in thalidomide for the treatment of immune system-related diseases.

Assessment of the uptake and mutagenicity of nickel chloride in Salmonella tester strains

NiCl 2 was examined for mutagenic activity in a number of Salmonella tester strains. Conditions were established where there was substantial uptake of the metal into the bacterial cells. However, even when the metal ion was apparently taken up, as determined by metal association with cells, there was a lack of mutagenic activity. These results suggest that nickel is unable to induce basepair or frameshift mutations in Salmonella tester strains and are discussed in relationship to the low binding affinity of Ni(II) for DNA.

Lack of mutagenic activity of crude and refined oils in the unicellular alga Chlamydomonas reinhardtii.

Over the past several years, an increasing number of studies have presented evidence for the mutagenicity and/or carcinogenic potential of petroleum-derived hydrocarbons. These most usually were obtained with individual hydrocarbons, and using either specialized bacterial strains (e.g. Ames' strains) or mammalian tissue preparations. While providing important insights into mutagenic mechanisms involving xenobiotic compounds, the relevance of these studies to the natural aquatic environment is not always evident. This applies especially to the mutagenic potential of water-soluble fractions of hydrocarbon mixtures, as in whole oils or in complex distillate fractions, and involving typical marine biota. Accordingly, the authors have examined the mutagenic potential of the water-soluble fractions of four oils (two crude oils and two refined oils) using the unicellular haploid alga Chlamydomonas reinhardtii.

Lack of mutagenic activity of malachite green in the mammalian spot test

Lack of mutagenic activity of malachite green in the mammalian spot test

Potent antiviral 2'-fluoro-arabinosyl pyrimidine nucleosides: lack of mutagenic activity.

The carcinogenicity of many drugs, such as antitumor agents, is a subject of growing concern. The newly developed pyrimidine nucleosides, 2'-fluoro-5-iodo-1-beta-D-arabinofuranosylcytosine (FIAC) and 2'-fluoro-1-beta-D-arabinofuranosyl-5-methyluracil (FMAU), have shown potent anti-herpes virus activity in tissue cultures, laboratory animals and man and an activity to inhibit the growth of certain tumor cell lines in vitro. Radioactivity of 14C-labeled FIAC and FMAU is incorporated into the DNA of normal and neoplastic mammalian tissues. However, we now report that FIAC and FMAU are inactive in a bacterial mutagenesis assay (Salmonella-microsome test) and in a mammalian cell mutagenesis assay employing V79 Chinese hamster cells in vitro. Both agents did not induce unscheduled DNA synthesis in primary Wistar rat hepatocytes in vitro.

Silver Sulfadiazine: Lack of Mutagenic Activity

Silver sulfadiazine was found to be devoid of mutagenic potential in a sensitive mutagenicity assay using Salmonella typhimurium. In view of the close relationship between mutagenicity in this system and carcinogenicity in animals, these findings suggest that silver sulfadiazine is apparently also devoid of carcinogenic properties.

3163. Negative Ames test for optical brighteners: McGregor, D. B. & Ainsworth, L. (1976). Lack of mutagenic activity in Salmonella typhimurium of four optical brighteners. Mutation Res.40, 169

3163. Negative Ames test for optical brighteners: McGregor, D. B. & Ainsworth, L. (1976). Lack of mutagenic activity in Salmonella typhimurium of four optical brighteners. Mutation Res.40, 169

Lack of mutagenic activity in Salmonella typhimurium of four optical brighteners

Lack of mutagenic activity in Salmonella typhimurium of four optical brighteners

The mutagenic activity of 1-alkyl-1-nitrosoureas and 1-alkyl-3-nitro-1-nitrosoguanidines

Abstract The mutagenic activities of five 1-alkyl-1-nitrosoureas and six 1-alkyl-3-nitro-1-nitrosoguanidines were tested and compared on Arabidopsis thaliana . All the nitrosoureas tested were active, whereas only methyl and ethyl derivatives of nitrosogunidines were. There was a tendency for the mutagenic effectiveness to decrease with increasing number of C-atoms in the alkl group. The nitrosoamides tested had a much higher mutagenic efficiency than X-rays, i.e. at the same level of induced mutations they caused less sterility. The possible reasons for the activity of nitrosoguanidines in Arabidopsis and their lack of mutagenic activity in barley are briefly discussed.