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T M Brooks

Publications and source records attributed to T M Brooks.

At least 19 recordsLinked to original sources
PubMed2006

Global biodiversity conservation priorities.

The location of and threats to biodiversity are distributed unevenly, so prioritization is essential to minimize biodiversity loss. To address this need, biodiversity conservation organizations have proposed nine templates of global priorities over the past decade. Here, we review the concepts, methods, results, impacts, and challenges of these prioritizations of conservation practice within the theoretical irreplaceability/vulnerability framework of systematic conservation planning. Most of the templates prioritize highly irreplaceable regions; some are reactive (prioritizing high vulnerability), and others are proactive (prioritizing low vulnerability). We hope this synthesis improves understanding of these prioritization approaches and that it results in more efficient allocation of geographically flexible conservation funding.

Animals↗
PubMed2003

Wilderness and biodiversity conservation.

Human pressure threatens many species and ecosystems, so conservation efforts necessarily prioritize saving them. However, conservation should clearly be proactive wherever possible. In this article, we assess the biodiversity conservation value, and specifically the irreplaceability in terms of species endemism, of those of the planet's ecosystems that remain intact. We find that 24 wilderness areas, all > or = 1 million hectares, are > or = 70% intact and have human densities of less than or equal to five people per km2. This wilderness covers 44% of all land but is inhabited by only 3% of people. Given this sparse population, wilderness conservation is cost-effective, especially if ecosystem service value is incorporated. Soberingly, however, most wilderness is not speciose: only 18% of plants and 10% of terrestrial vertebrates are endemic to individual wildernesses, the majority restricted to Amazonia, Congo, New Guinea, the Miombo-Mopane woodlands, and the North American deserts. Global conservation strategy must target these five wildernesses while continuing to prioritize threatened biodiversity hotspots.

Animals↗
PubMed1999

Transgenic mouse mutation assay systems can play an important role in regulatory mutagenicity testing in vivo for the detection of site-of-contact mutagens.

Transgenic mouse mutation assays, such as MutaMouse (lacZ, CD2F1) and Big Blue (lacI, B6C3F1), afford the opportunity to evaluate the mutagenic potential of chemicals in any target organ in vivo. This paper discusses published data collected from the analysis of the skin, stomach and lung DNA after topical, oral and inhalation exposure, respectively. These data indicate that both MutaMouse and Big Blue should play an important part in the evaluation of genotoxicity in vivo, particularly where the endpoint or target tissue available in the more conventional tests is inappropriate. It is concluded that there is a distinct role for this type of assay in genetic toxicology testing. For substances applied to the skin or dosed orally or by inhalation and which are unlikely to reach either the bone marrow or the liver, then data derived from these assays may be more relevant to an assessment of possible risk to man than the currently used unscheduled DNA synthesis in liver and cytogenetics assays in bone marrow or peripheral blood.

Animals↗
PubMed1998

Benzo[a]pyrene site of contact mutagenicity in skin of Muta Mouse.

Benzo[a]pyrene (BP) has been investigated for the ability to induce mutation at the site of contact. Skin painting treatments with BP caused a time-dependent and statistically significant increase in mutation frequency (MF) in the treated areas of skin. The MF exceeded 500 x 10(-6) 21 days after either 1 x 25 or 5 x 5 micrograms treatments. Increases to > 700 x 10(-6) were seen when doses of 1 x 50 or 5 x 10 micrograms were used. Neither the liver nor the lung showed any increase in mutation frequency after 21 days in animals exposed to the 5 x 10 micrograms treatment regime. It is concluded that following topical administration, BP is able to induce mutation in the skin at the site of application, but not in either the lung or liver.

Administration, Cutaneous↗
PubMed1997

The detection of gene mutation in the tubular sperm of Muta Mice following a single intraperitoneal treatment with methyl methanesulphonate or ethylnitrosourea.

Transgenic mouse assays, such as Muta Mouse, provide a method to predict the potential target organ carcinogenicity of chemical compounds. As part of a collaborative study, the effects of the direct-acting mutagens, methyl methanesulphonate (MMS) and ethylnitrosourea (ENU), were investigated for gene mutation in the tubular sperm of Muta Mice testes after a single intraperitoneal exposure. Groups of male Muta Mice were dosed intraperitoneally with either 1/15 M phosphate buffer, pH 6.0 (vehicle control), 40 mg/kg methyl methanesulphonate (MMS) or 150 mg/kg ethylnitrosourea (ENU). The animals were sacrificed 14 days after the single dose. Mutation frequencies were determined in tubular sperm DNA. The results showed a mean mutation frequency (MF) of 2.1 x 10(5) (64 mutants per 3.05 x 10(6) PFU) for the 10 vehicle-treated mice, a mean MF of 2.8 x 10(5) (78 mutants per 2.75 x 10(6) PFU) for the 10 MMS-treated mice and a mean MF of 9.1 x 10(5) (194 mutants per 2.14 x 10(6) PFU) for the 8 ENU-treated mice; this latter value representing a 4.5-fold increase over the vehicle control values.

Animals↗
PubMed1996

Detection of gene mutation in skin, stomach and liver of MutaMouse following oral or topical treatment with N-methyl-N'-nitro-N-nitrosoguanidine or 1-chloromethylpyrene: some preliminary observations.

Transgenic mouse assays, such as MutaMouse, provide a method to predict the potential target organ carcinogenicity of chemical compounds. As part of a validation study, the effects of the direct-acting mutagens, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 1-chloromethyl-pyrene (CMP), were investigated for gene mutation in the tissues of MutaMice after a single oral or topical exposure. MNNG (50 or 100 mg/kg) or CMP (25 or 50 mg/kg) were administered as a single oral dose and the mice killed after 3, 7 or 10 days. Mutation frequencies were determined in stomach DNA from both MNNG and CMP-treated animals and in liver DNA from the MNNG-treated animals only. The results, although obtained from a limited number of animals, consistently showed that MNNG increased the mutation frequency in stomach DNA, but not apparently in liver DNA, at each exposure time; no clear increase in mutation frequency was seen in the stomach DNA of CMP-treated animals. Also, MNNG (250 or 500 micrograms) or CMP (5 or 10 micrograms) in acetone were applied as a single dose to the shorn skin of mice 7, 14 or 21 days prior to death. A positive control group was similarly given dimethyl-benz[a]anthracene (DMBA, 40 micrograms) and sacrificed after 14 days. Mutation frequencies were determined in the skin DNA extracted from all animals and in the stomach DNA from MNNG-painted animals only. The results, again obtained from a limited number of animals, clearly showed that all test compounds consistently increased the mutation frequency of skin DNA and that these increases were far greater in the DMBA- and MNNG-treated mice than the CMP-treated mice. No apparent increases were seen in the stomach DNA from the MNNG-painted mice.

Administration, Oral↗
PubMed1995

The detection of gene mutation in transgenic mice (Muta Mouse) following a single oral dose of 2-acetylaminofluorene.

Transgenic mouse assays, such as Muta Mouse, provide a method to predict the potential target organ carcinogenicity of chemical compounds. As part of a validation study, 2-acetylaminofluorene was administered as a single oral dose of either 50 or 100 mg/kg. The mice were killed 3, 7, 14, 28, 56 or 112 days after this single treatment. Mutation frequencies were determined in liver DNA. The results showed that a mutagenic response was observed in the mice treated at the highest dose (100 mg/kg) and this increase was expressed from 28 up to 112 days after the single exposure.

2-Acetylaminofluorene↗
PubMed1995

Evaluation of modified bacterial mutagenicity assays for the genotoxicity testing of mineral oils.

A modified bacterial mutagenicity assay based on the Ames Salmonella/mammalian microsome test has been developed for application in the genotoxicity testing of mineral oils. The assay uses washed microsomes from rat liver in place of S9 fraction in order to increase the sensitivity of detection of genotoxicity. The modified assay was used to test a series of oils for which skin carcinogenicity bioassay data in mice were available. Oils were tested as emulsions in water using Tween 80 as a dispersant. A mutagenicity index for each oil was obtained using non-linear regression analysis of data from the dose-response curve. The results showed an empirical correlation between increasing mutagenicity index, carcinogenicity and the polycyclic aromatic hydrocarbon content of the oils. The washed-microsome assay was also compared with modified Ames assays developed by Blackburn et al. (Cell Biol. Toxicol., 1, 40, 1984; Cell Biol. Toxicol., 2, 63, 1986) which employed increased levels of S9 (rat and hamster liver) to test dimethyl sulphoxide extracts of oils. The washed-microsome assay can be used for the testing of whole oils rather than extracts which are necessary for the modified Ames assay. It is recognised that the determinants of carcinogenic activity in vivo include promoting activity which such assays are unable to detect. Nevertheless, such modified bacterial assays may be a useful prescreen since genotoxicity is recognised as a key initial step in carcinogenesis.

Animals↗
PubMed1995

The use of a streamlined bacterial mutagenicity assay, the MINISCREEN.

A streamlined bacterial mutagenicity assay, the MINISCREEN, was developed to enable the rapid screening of a large number of chemical compounds on a purely qualitative basis. Experiments with a series of known carcinogens/mutagens and non-carcinogens/mutagens showed a good correlation with conventional bacterial mutagenicity assays (Ames tests), and the subsequent testing of over 300 candidate agricultural chemicals and over 100 industrial chemicals has proven its value as a screening method.

Animals↗
PubMed1988

The genetic toxicology of some hydrocarbon and oxygenated solvents.

Two hydrocarbon solvents (heptane and Special Boiling Point Spirit 100/140) and eight oxygenated solvents [methyl ethyl ketone, methyl isobutyl ketone, diacetone alcohol, di-isobutyl ketone, isopropyl ether, hexylene glycol, secondary butyl alcohol and ME 6K (pentoxone)] have been tested for genotoxic activity. The solvents were tested in bacterial mutation assays, a yeast assay for mitotic gene conversion and in cultured mammalian cells (either rat liver or Chinese hamster ovary) for structural chromosome damage. All of the solvents gave a negative response in the bacterial mutation assays and the yeast mitotic gene conversion assay. In the rat liver chromosome assay, diacetone alcohol evoked a weak positive response, the remaining solvents gave a negative response.

Alcohols↗
PubMed1987

Microbial mutagenicity studies with (Z)-1,3-dichloropropene.

This study has confirmed that the direct mutagenicity previously observed when S. typhimurium TA100 was treated with (Z)-1,3-dichloropropene (DCP) was in fact due to trace impurities. These impurities result from autoxidation of (Z)-1,3-DCP and have now been identified. Both (Z)- and (E)-2-chloro-3-(chloromethyl)oxiranes (DCP oxides) were identified as significant products during this autoxidation. The mutagenic impurities formed by autoxidation were completely removed by adsorption chromatography on silicic acid. (Z)-1,3-DCP purified in this way had no direct-acting mutagenicity towards S. typhimurium TA100. However, (Z)-1,3-DCP undergoes mono-oxygenase-catalysed conversion into bacterial mutagens in the presence of S9 fraction or washed microsomes from rat liver. The glutathione-linked conjugation systems of mammalian tissues provided efficient protection against this indirect mutagenic action. However, the low concentration of glutathione in standard bacterial mutagenicity assays limits the glutathione S-alkyl transferase-catalysed detoxification of (Z)-1,3-DCP and its primary bioactivation product(s). When the concentration of glutathione was adjusted to the normal physiological concentration, the mono-oxygenase-dependent mutagenic action of (Z)-1,3-DCP was virtually eliminated. These results therefore are consistent with the view that bacterial mutation assays are only qualitative indicators of potential mammalian genotoxicity.

Allyl Compounds↗
PubMed1985

Genotoxicity studies with mineral oils; effects of oils on the microbial mutagenicity of precursor mutagens and genotoxic metabolites.

In vitro genotoxicity assays are extensively used to predict carcinogenic activity in vivo. The standard microbial mutagenicity assays however often fail to yield positive results with mineral oils which are carcinogenic to mice in long-term skin-cancer studies. A comprehensive programme of studies has therefore investigated the basis of this apparently anomalous behaviour. This investigation has addressed the possible effects of oils on the bioactivation of precursor mutagens and the disposition of mutagenic metabolites by studying the microbial mutagenicity of selected precursor mutagens (benzo[a]pyrene, benzo[a]anthracene, 2-aminoanthracene and 2-naphthylamine) and intrinsically reactive mutagens [+/- )-benzo[a]pyrene-4,5-oxide and (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene) in the presence and absence of mineral oils. Notably the mutagenicity associated with the deliberate additions of these mutagens or precursor mutagens to oils was readily detected by the microbial assays. The mutagenicity of only one of the precursor mutagens, benzo[a]pyrene, was significantly reduced by the oils, and then only in the standard plate-incorporation assay. Interestingly the degree of suppression appeared to be related to the polycyclic aromatic hydrocarbon content of the oils. In the case of 2-aminoanthracene large enhancements in its mutagenicity were observed in the presence of oils. These latter findings appear to be due to effects of oils on the bioactivation of precursor mutagens rather than on the disposition of their bioactivation products. The mutagenicity of intrinsically reactive mutagens, of a type generated by bioactivation of polycyclic aromatic hydrocarbons, was not significantly reduced in the presence of mineral oils. This indicates that it is unlikely that components in oils trap or facilitate the deactivation of ultimate mutagens whether these pre-exist in the oil or are formed from precursors by bioactivation in the in vitro test system. Viewed overall these results suggest that mineral oils judged to be carcinogenic on the basis of in vivo studies in mouse skin may possess only very weak genotoxic potential. While this potential is likely to be a prerequisite for carcinogenic action, the current results cause attention to be focussed on other factors, e.g. promotion, as potentially important determinants of the carcinogenic potencies of mineral oils in mouse skin.

2-Naphthylamine↗
PubMed1984

The protective action of glutathione on the microbial mutagenicity of the Z- and E-isomers of 1,3-dichloropropene.

The Z(cis)- and E(trans)-isomers of 1,3-dichloropropene (DCP), in confirmation of previous reports, caused dose-dependent increases in the numbers of reverse mutations in Salmonella typhimurium TA100 in the presence and absence of a 9000 X g supernatant fraction (S9) from the livers of Aroclor-treated rats. The relevance of these findings to mammals is uncertain, not least because of major differences in the metabolism of the DCPs in the microbial assay systems and in vivo. For example, (Z)-DCP is efficiently detoxified in mammals by the operation of a glutathione (GSH)-dependent S-alkyl transferase. It is possible that such detoxification could proceed only very slowly in the microbial assays because the concentrations of GSH could be severely rate-limiting even in those assays fortified by the addition of S9. The results obtained in the current study demonstrate a dramatic reduction in the microbial mutagenicity of both (Z)- and (E)-DCP when the concentration of GSH in the microbial assays was adjusted to a normal physiological concentration (5 mM). However, this protective action of GSH was at least as effective in the absence of S9 as in its presence, suggesting that it was not mediated by mammalian GSH transferase. There appears to be little or no GSH alkyl or aryl transferase in the cytosol of S. typhimurium TA100, but intracellular GSH is present at a concentration similar to that found in mammalian cells. Since the uncatalysed reaction between the DCPs and glutathione is relatively slow, the effect is not due simply to their destruction by GSH. It is possible that a physiological concentration of extracellular GSH maintains the intracellular GSH in a reduced form in which its nucleophilic thiol group competes effectively with the nucleophilic centres in the bacterial DNA for the haloalkenes. The current results highlight the efficiency of GSH-linked systems in affording protection against the genotoxic action of the DCPs. It may be presumed that their operation would exert a major limiting effect on the genotoxicity of (Z)- and (E)-DCP in mammals.

Allyl Compounds↗
PubMed1983

Genotoxicity studies with a blend of zinc dialkyldithiophosphate lubricant additives.

The mutagenic activity of a blend of primary zinc dialkyldithiophosphate lubricant additives suspended in process oils and a blend of the process oils alone was investigated in agar layer cultures of Salmonella typhimurium TA1535, TA1537, TA1538, TA98 and TA100, both with and without the incorporation of a rat liver microsomal activation system (S9). Zinc dimethyldithiocarbamate was tested as a structurally-related model bacterial mutagen, and, in additional control experiments, the mutagenic activity of zinc dimethyldithiocarbamate and benzo[a]pyrene was investigated in combination with the blend of process oils in selected bacterial tester strains. Transformation frequencies of BHK cells were determined by colony growth in soft agar culture following treatment with a blend of the zinc dialkyldithiophosphate lubricant additives suspended in process oils, a blend of the process oils, 7,12-dimethylbenzanthracene, both in the presence and in the absence of a blend of the process oils, or zinc dimethyldithiocarbamate. All experiments incorporated a rat liver microsomal activation system (S9). Application of a blend of the zinc dialkyldithiophosphate additives or a blend of the process oils used in their manufacture did not increase the reverse mutation frequencies of Salmonella typhimurium TA1535, TA1537, TA1538, TA98 or TA100, or significantly increase the transformation frequency of BHK cells under the experimental conditions described. Zinc dimethyldithiocarbamate increased the reverse mutation frequency in some bacterial tester strains, but did not significantly increase the transformation frequency of BHK cells under the described experimental conditions. The addition of the blend of the process oils in combination with the control materials, zinc dimethyldithiocarbamate or benzo[a]pyrene had an inhibitory effect on the mutagenic activity at high doses of each in the bacterial assays, and in the BHK assay the transforming ability of 7,12-dimethylbenzanthracene was suppressed in the presence of the blend of the process oils. Thus, the additive materials showed no evidence of genotoxic activity in the bacterial mutation assays, or in the BHK transformation assay under the experimental conditions described.

Animals↗
PubMed1983

Mutagenicity and in vivo disposition of biliary metabolites of benzo(a)pyrene.

Rabbits and rats administered [3H]benzo(a)pyrene (BP; 40 mumol/kg, i.v.) excreted, via the bile, metabolites which increased reverse gene mutation frequency in Salmonella typhimurium TA98 when incubated with beta-glucuronidase. Glucuronic acid conjugates of BP 4,5-diol, BP 1,6-, 3,6- and 6,12-quinones were detected in rat bile with low levels of 3- and 9-OH BP and BP 7,8- and 9,10-diols. In rabbits BP 9,10-diol was the major aglycone along with smaller amounts of BP 1,6- and 3,6-quinones, BP 4,5- and 7,8-diols and 3- and 9-OH BP. Qualitatively similar metabolic profiles were found when animals were given 3 mumol/kg [3H]BP. When 3H-labelled biliary metabolites, which contained the mutagenic component, were administered intraduodenally to rats, radioactivity reached the systemic circulation but DNA adducts were not detectable (less than 0.03 pmol/mg DNA) in tissues (intestinal wall, liver and lung) exposed to the reabsorbed metabolites.

Animals↗