Mutation Research\/genetic Toxicology 

About: Mutation Research\/genetic Toxicology is an academic journal published by Elsevier BV. The journal publishes majorly in the area(s): Micronucleus test & Genotoxicity. It has an ISSN identifier of 1383-5718. Over the lifetime, 2002 publications have been published receiving 61951 citations.

Human cell mutagenicity of oxygenated, nitrated and unsubstituted polycyclic aromatic hydrocarbons associated with urban aerosols.

Abstract: Polycyclic aromatic compounds (PAC) are ubiquitous pollutants in urban air that may pose risks to human health. In order to better assess the health risks associated with this class of compounds, a total of 67 PAC that either have been identified (55) or are suspected to be present (12) in urban aerosol samples were tested for mutagenicity in a forward mutation assay based on human B-lymphoblastoid cells. The cell line used (designated h1A1v2) constitutively expresses the cytochrome P4501A1, which is known to be necessary for the metabolism of many promutagens. The PAC tested included 39 polycyclic aromatic hydrocarbons (PAH). 19 oxygen-containing PAH (oxy-PAH) and nine NO2-substituted PAH (nitro-PAH). A total of 26 PAH were mutagenic. In comparing the minimum mutagenic concentrations of the mutagenic PAH with that of benzo[a]pyrene (B[a]P) it was found that dibenzo[a,l]pyrene (DB[al]P), cyclopenta[c,d]pyrene (CPP), naphtho[2,1-a]pyrene, dibenzo[a,e]pyrene (B[a]P) and 1-methylbenzo[a]pyrene were 24 +/- 21, 6.9 +/- 4.2, 3.2 + 3.0, 2.9 +/- 2.9 and 1.6+/- 1.4 times, respectively, more mutagenic than B[a]P, and that dibenzo[a,k]fluoranthene and B[a]P were approximately equally mutagenic. The 19 other mutagenic PAH were between approximately 2 and approximately 1800 times less mutagenic than B[a]P. Of the oxy-PAH tested only phenalenone, 7H-benz[d,e]anthracen-7-one, 3-nitro-6H-dibenzo[b,d]pyran-6-one, cyclopenta[c,d]pyren-3(4H)-one, 6H-benzo[c,d]pyren-6-one (BPK) and anthanthrenequinone were mutagenic; however, with the exception of BPK, these were over 50 times less active than B[a]P, BPK was approximately 3 times less active than B[a]P. Seven of the nitro-PAH were mutagenic including 9-nitroanthracene, 1-nitropyrene, 2-nitrofluoranthene, 3-nitrofluoranthene, 1,3-dinitropyrene, 1,6-dinitropyrene (1,6-DNP) and 1,8-dinitropyrene. 1,6-DNP was approximately 4 times less active than B[a]P; the six other mutagenic nitro-PAH were between 20 and 380 times less active than B[a]P. These results are discussed in terms of their relevance for determining the most important mutagens in ambient air. Based on reported concentrations of PAC in ambient aerosols, it is possible that CPP, DB[ae]P, DB[al]P and BPK could account for a greater proportion of the mutagenicity than B[a]P in some aerosols.

Chemical structure, Salmonella mutagenicity and extent of carcinogenicity as indicators of genotoxic carcinogenesis among 222 chemicals tested in rodents by the U.S. NCI/NTP.

Abstract: A survey has been conducted of 222 chemicals evaluated for carcinogenicity in mice and rats by the United States NCI/NTP. The structure of each chemical has been assessed for potential electrophilic (DNA-reactive) sites, its mutagenicity to Salmonella recorded, and the level of its carcinogenicity to rodents tabulated. Correlations among these 3 parameters were then sought. A strong association exists among chemical structure (S/A), mutagenicity to Salmonella (Salm.) and the extent and sites of rodent tumorigenicity among the 222 compounds. Thus, a approximately 90% correlation exists between S/A and Salm. across the 115 carcinogens, the 24 equivocal carcinogens and the 83 non-carcinogens. This indicates the Salmonella assay to be a sensitive method of detecting intrinsic genotoxicity in a chemical. Concordance between S/A and Salm. have therefore been employed as an index of genotoxicity, and use of this index reveals two groups of carcinogens within the database, genotoxic and putatively non-genotoxic. These two broad groups are characterized by different overall carcinogenicity profiles. Thus, 16 tissues were subject to carcinogenesis only by genotoxins, chief among which were the stomach, Zymbal's glands, lung, subcutaneous tissue and circulatory system. Conclusions of carcinogenicity in these 16 tissues comprised 31% of the individual chemical/tissue reports of carcinogenicity. In contrast, both genotoxins and non-genotoxins were active in the remaining 13 tissues, chief among which was the mouse liver which accounted for 24% of all chemical/tissue reports of carcinogenicity. Further, the group of 70 carcinogens reported to be active in both species and/or in 2 or more tissues contained a higher proportion of Salmonella mutagens (70%) than observed for the group of 45 single-species/single-tissue carcinogens (39%). 30% of the 83 non-carcinogens were mutagenic to Salmonella. This confirms earlier observations that a significant proportion of in vitro genotoxins are non-carcinogenic, probably due to their non-absorption or preferential detoxification in vivo. Also, only 30% of the mouse liver-specific carcinogens were mutagenic to Salmonella. This is consistent with tumors being induced in this tissue (and to a lesser extent in other tissues of the mouse and rat) by mechanisms not dependent upon direct interaction of the test chemical with DNA. Detection of 103 of the 115 carcinogens could be achieved by use of only male rats and female mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Fish micronuclei for assessing genotoxicity in water

Abstract: Micronucleus assays with fish have been shown to be useful in vivo techniques for genotoxicity testing, and show potential for in situ monitoring of water quality In this paper, we review the literature on the clastogenic effects of chemical and physical agents on fish cells, with emphasis on the induction of micronuclei in teleosts Included in the review is a description of the mechanisms for formation of micronuclei in cells, and a summary of the various techniques that have been used for micronucleus analysis in fish This review is directed to assisting laboratories in the development of fish genotoxicity assays for water quality monitoring

Carcinogenic N-nitrosamines in the diet: occurrence, formation, mechanisms and carcinogenic potential.

Abstract: Nitrosamines form a large group of genotoxic chemical carcinogens which occur in the human diet and other environmental media, and can be formed endogenously in the human body. N-Nitroso compounds can induce cancer in experimental animals. Some representative compounds of this class induce cancer in at least 40 different animal species including higher primates. Tumours induced in experimental animals resemble their human counterparts with respect to both morphological and biochemical properties. Extensive experimental, and some epidemiological data suggest that humans are susceptible to carcinogenesis by N-nitroso compounds and that the presence of these compounds in some foods may be regarded as an aetiological risk factor for certain human cancers including cancers of the oesophagus, stomach and nasopharynx.