Indirect-acting Mutagens Research Articles

Detection of short-lived mutagens in welding fumes with a culture of Salmonella typhimurium TA100 in a microimpinger

Fifteen kinds of commonly consumed Thai vegetables were sequentially extracted with hexane, chloroform and methanol, and then tested for antimutagenic activities against direct-acting (AF-2 and NaN3) and indirect-acting (AFB1 and B(a)P) mutagens using Ames' Salmonella mutagenicity test with Salmonella typhimurium TA100 as tester strain. It was found that only the methanol extract of neem leaves contain weak antimutagen inhibiting the mutagenicities of both direct-acting mutagens. Interestinglly, all vegetables studied were found to contain chemical compounds, mainly nonpolar ones, capable of inhibiting the mutagenicity of AFB1, while only some vegetables contain chemical compounds capable of inhibiting the mutagenicity of B(a)P, which is also an indirect-acting mutagen. Studies on anticarcinogenic potentials demonstrated that Thai bitter gourd fruits, but not sweet basil leaves, at the concentration of 6.25% and 12.5% in the diet, partially inhibited DMBA-induced mammary gland carcinogenesis in female Sprague-Dawley rats when fed to the animals 2 weeks prior to DMBA. Results in the present study therefore demonstrated that most Thai vegetables contain antimutagens inhibiting the mutagenicity of some indirect-acting mutagen, particularly AFB1. The mechanism of their antimutagenicity may probably be the inhibition of the activity of metabolic-activating enzymes in rat liver homogenates. Very interestingly, our results clearly reveal that Thai bitter gourd fruits, which possess Phase II enzymes inducing property, as well as the ability to reduce Phase I enzyme activities in rat liver, contain some anticarcinogens or chemopreventive agents. However, sweet basil leaves that possess both Phase I and Phase II enzyme-inducing properties may not contain any anticarcinogen, at least against DMBA-induced mammary gland carcinogenesis.

An analysis of the efficacy of bacterial DNA-repair assays for predicting genotoxicity

Several bacterial DNA-repair tests have been developed as rapid assays for genotoxicity. In these systems, a positive result is generally considered as evidence for interaction of a chemical with DNA and an indication of carcinogenicity. Recently much data have been published on the responses to suspect carcinogens of such systems in the presence and absence of added exogenous metabolising fractions. An analysis of this literature is presented and it is concluded that bacterial repair tests provide a useful prediction of potential carcinogenicity especially for certain classes of compounds. However, a significant number of procarcinogens and indirect-acting mutagens does not require mammalian metabolism in order to exhibit activity in repair assays. Possible reasons for this discrepancy as well as recommendations concerning the value of bacterial repair systems in carcinogenicity screening are discussed.

Mutagenicity in Salmonella typhimurium mutants of serum extracts from airborne particulates

Airborne particulates collected from urban and non-urban air were extracted with calf serum or benzene, and their mutagenic potencies were evaluated in the Salmonella reversion assay. The serum extracts were mutagenic to strains TA98 and TA100 and contained both direct- and indirect-acting mutagens. Mutagenic activities for TA98 recovered from the particulates by serum or benzene extraction were much less in the serum extracts than in the benzene extracts. There was no significant difference in mutagenic potencies of the extracts between the urban and non-urban particulates, irrespective of the presence of S9 mix. The calculated mutagenic activities per m 3 of air, however, were greater for urban air than for non-urban air, because of higher concentration of particulates in urban air than in non-urban air. Serum effectively reduced both direct and indirect mutagenic activities of the benzene extracts except for an insufficient reduction in direct mutagenicity at a high dose of benzene extracts. These findings suggest that serum could contribute greatly to decrease the mutagenicity of airborne particulates by mechanisms such as less efficient solubilization of mutagenic components and inactivation by protein binding. Biological availability of mutagens, therefore, should be considered for evaluation of actual mutagenic hazard by airborne particulates.

Sister-chromatid exchanges induced in vitro by cyclophosphamide without exogenous metabolic activation in lymphocytes from three mammalian species

The induction of sister-chromatid exchanges (SCEs) by cyclophosphamide (CP) in human, rat and rabbit lymphocytes was studied in vitro without exogenous metabolic activation. In contrast with published reports, CP induced SCEs in lymphocytes from all three species, indicating that cultured lymphocytes possess the metabolic capacity to convert this indirect-acting mutagen.

Influence of rat lung and liver homogenates on the mutagenicity of diesel exhaust particulate extracts

Diesel exhaust particles collected from an automobile operated on a chassis dynomometer were extracted with dichloromethane and evaluated for mutagenicity in Salmonella typhimurium. The extracts were mutagenic to strains TA-100, TA-98, TA-1538, and TA-1537 and contained both direct and indirect-acting mutagens. The promutagens in the extract were activated by the addition of Aroclor 1254 induced and uninduced rat liver S-9, but not uninduced lung S-9. All three S-9 preparations, as well as Aroclor induced liver S-9 without NADP, bovine serum albumin, and fetal calf serum, significantly decreased the direct mutagenicity in TA-100 suggesting that protein binding of mutagenic components was at least partially responsible. Results of studies using the mixed-function oxidase inhibitor SKF 525-A suggest a minor role of metabolism in detoxifying mutagens in the extract. The inability of lung S-9 to activate promutagens in the extract and protein binding of direct-acting mutagens may be important modifying factors to consider in estimating the potential human inhalation health hazards of diesel particulate exhaust emissions.