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J Ashby

Publications and source records attributed to J Ashby.

377 records · Page 21Linked to original sources
PubMedDate not supplied

Carcinogenicity bioassay of 4-chloromethylbiphenyl (4CMB), 4-hydroxymethylbiphenyl (4HMB) and benzyl chloride (BC) on mouse skin: interim (7 month) report.

4CMB, 4HMB, BC of benzo[a]pyrene (BP, positive control) dissolved in toluene have been applied twice weekly to the shaved dorsal region of groups of 20 Alderley Park Swiss albino mice. After 7 months of treatment, 6/20 of the BP test group were confirmed as having developed squamous cell carcinoma of the skin. However, none of the animals in the test groups appeared to have been affected by the test chemicals. This interim observation was supplemented by intercurrent sacrifice of 1 animal from each of the test groups, followed by histopathological examination of sections of the subcutaneous tissue. No neoplastic changes were discerned.

Animals↗
PubMedDate not supplied

An assessment of the in vivo rat hepatocyte DNA-repair assay.

The in vivo rat hepatocyte autoradiographic assay for unscheduled DNA synthesis (UDS) described by Mirsalis et al, and its in vitro counterpart described earlier by Williams have been employed by us for 4 years. Our experience is that the in vivo assay performs as described in the literature. We have therefore concentrated in this initial paper on the key practical factors we have found to govern the assay sensitivity and reproducibility. This has been achieved by a discussion of the assay performance with two potent rat hepatocarcinogens [the novel azo compound 6-dimethylaminophenylazobenzthiazole (6BT) and the reference agent 2-acetylaminofluorene (2AAF)] and a non-carcinogen of similar structure to 6BT [5-dimethylaminophenylazoindazole (51)]. Assay responses were compared with the effect of these chemicals in the Salmonella mutation assay. We conclude that the in vivo liver UDS assay has a critical role to play as a complement to rodent bone marrow cytogenic assays when conducting assessment studies on agents defined as genotoxic in vitro. However, the in vivo assay is resource-consuming and false results could consequently arise due to incomplete evaluations. Methods to counteract this danger are discussed and criteria for assessing weak UDS responses are suggested.

2-Acetylaminofluorene↗
PubMedDate not supplied

Chloracetamide-N-metholol: an example of an in vitro and in vivo clastogen which is non-mutagenic to Salmonella.

The industrial biocide chloracetamide-N-metholol (CAM) has been shown to be non-mutagenic to 6 strains of Salmonella using both the plate-incorporation and a pre-incubation test protocol. Its biocidal activity is unlikely to have influenced these results since Kathon 886, a more potent biocide, was concomitantly detected as mutagenic to strain TA100. In contrast, CAM was weakly clastogenic to human lymphocytes cultured in vitro and elicited a positive response in the mouse bone marrow micronucleus test when assayed using the intraperitoneal, but not the oral route of administration. A positive response was concomitantly observed for the rodent carcinogen and formaldehyde-releasing agent hexamethylphosphoramide (HMPA) in these 2 clastogenicity assays. Data are presented showing the slow hydrolysis of CAM to formaldehyde in vitro, and both [carbonyl-14C]CAM and [metholol-14C]CAM have been shown to interact covalently with calf-thymus DNA in vitro. It is concluded that CAM may be a direct-acting carcinogen to rodents, but that both the qualitative and quantitative outcome of its bioassay for carcinogenicity will be influenced critically by the bioassay protocol adopted; in particular, by the route of administration selected. These findings emphasize the need to complement the Salmonella gene-mutation assay with an in vitro assay for the induction of chromosomal aberrations if in vivo genotoxins are to be detected efficiently in vitro.

Acetamides↗
PubMedDate not supplied

Reflections on the declining ability of the Salmonella assay to detect rodent carcinogens as positive.

It is suggested that urgent attempts should be made to define and gain general agreement for the existence of two classes of animal carcinogen, those which are genotoxic and those which are not. In the absence of such a step, attempts to validate in vivo genotoxicity assays, and to derive a meaningful structure-activity database for chemical carcinogenesis, will be frustrated. These suggestions are supported by the preliminary findings of a detailed analysis of the carcinogen database accrued by the United States National Toxicology Program. The possibility that many non-genotoxic carcinogens should be regarded as tumour-promoting agents is considered.

Animals↗
PubMedDate not supplied

Lack of mutagenicity to S. typhimurium of neopentyl bromide and pentaerythrityl tetrachloride: relation to chemical structure.

Neopentyl bromide and pentaerythrityl tetrachloride were shown here to be non-mutagenic to 7 strains of Salmonella typhimurium. These inactivities are reflected in the inability of either compound to produce a colour reaction in the chemical alkylation test of Epstein (4-nitrobenzylpyridine, NBP). It is suggested that the lack of biological reactivity of these two alkyl halides is due to steric crowding of the halogen group. These findings are significant within the context of the potent mutagenicity of mono-haloalkanes in general. The similarity between the odour of pentaerythrityl tetrachloride and camphor is discussed.

Chemical Phenomena↗
PubMedDate not supplied

Mutation spectrum of a binary mixture of mutagens (methapyrilene and sodium azide) in strain TA1535 of Salmonella.

Methapyrilene (MP) is a rat-liver carcinogen and cocarcinogen that exhibits a narrow spectrum of mutagenic activity in Salmonella typhimurium, inducing only a 2-fold increase in revertants only in the base-substitution strain TA1535; it also enhances the mutagenic activity of sodium azide (NaN3) in the same strain. To examine the effects of MP at the molecular level, we used the colony probe hybridization procedure developed by Cebula and Koch (Mutation Res., 229 (1990) 79-87) to identify the base substitutions in approximately 800 background, MP-, NaN3-, and MP + NaN3-induced revertants of the hisG46 allele of strain TA1535. The predominant mutation in all 4 mutation spectra was a CCC-->CTC transition. The results suggest a mechanism by which MP enhances the infidelity of the DNA replication complex or inhibits a DNA repair or proofreading function, resulting in the production of more of the same error that occurs normally and that is also induced by NaN3. Such a mechanism might be the basis for the carcinogenic and cocarcinogenic activities of MP. To our knowledge, this is the first report of the molecular analysis of mutants produced by exposure of cells to a binary mixture of mutagens.

Azides↗
PubMedDate not supplied

Water precautions in children with tympanostomy tubes.

PURPOSE: The necessity and effectiveness of taking precautions around water with children who have tympanostomy tubes is a source of some controversy among otolaryngologists. This study was undertaken to survey the practice standards of otolaryngologists treating these children. MATERIALS AND METHODS: A total of 1,266 board-certified otolaryngologists practicing (mean 14.8 years in practice) in the southern and eastern United States were surveyed to determine current recommendations. RESULTS: Among those surveyed, 13.1% forbid children with tympanostomy tubes from swimming, whereas 3.1% feel that no water precautions are needed. Limitations are placed in the depth of swimming by 68% and the type of swimming water by 18%. The most commonly recommended form of protection is the use of ear plugs, which is favored by 53.4%. Liberalization of recommendations concerning the need for water precautions was noted by 79% of respondents who cited personal experience as the single most influential factor. An overwhelming percentage of respondents indicated they would be willing to alter their current practice based on new information generated from a clinical trial. CONCLUSION: This survey demonstrates that diversity of opinion does exist among otolaryngologists relative to their recommendations for water precautions after placement of tympanostomy tubes. This survey demonstrates the need for a prospective randomized clinical trial designed to address this issue.

Child↗
PubMedDate not supplied

The genotoxicity of sodium saccharin and sodium chloride in relation to their cancer-promoting properties.

The literature indicates that sodium saccharin is non-reactive to DNA and inactive as a gene mutagen in vitro. At elevated dose levels it is capable of producing structural disturbances in eukaryotic chromosomes in vitro, and it shows intermittent activity as a very weak germ-cell and somatic-cell mutagen in vivo. Its possible mode of action in these respects is speculated on and related to its ability to promote bladder tumours in rats at elevated dose levels. A review of the toxicology of sodium chloride reveals a profile of genotoxic activities almost identical to that of sodium saccharin. It is suggested that the recorded genotoxic and cancer-promoting activities of these chemicals will only become apparent at elevated dose levels that define them as significant contributors to the biological medium (solvent) rather than as trace xenobiotic toxins (solutes). The possible activity of acid saccharin, or of its potassium, calcium and ammonium salts, as ionic genotoxins requires urgent evaluation.

Animals↗
PubMedDate not supplied

The value and limitations of short-term genotoxicity assays and the inadequacy of current criteria for selecting chemicals for cancer bioassays.

The Salmonella gene mutation assay is established as the primary in vitro test for genotoxicity. It does not, however, detect all known genotoxic carcinogens, and several mammalian cell genotoxicity assays are now used to complement the Salmonella test--the most usual being cytogenetic analysis in vitro. Use of these two tests provides an adequate screen for genotoxins, but leaves undetected a variety of weak, DNA-unreactive animal carcinogens such as DDT, saccharin and diethylhexyl phthalate. A reappraisal of the present confused situation examines the underlying problems and options for action. It is suggested that the most effective way of focussing resources on the detection of possible new human carcinogens involves in vitro evaluation of genotoxicity, followed where appropriate by further evaluation in vivo, with urgent attention being paid to the methods currently used to select chemicals for cancer bioassays and to the resolution of the current debate on the validity of some recent classifications of carcinogenicity.

Animals↗
PubMedDate not supplied

The mutagenic and cell transforming properties of shikimic acid and some of its bacterial and mammalian metabolites.

Known and proposed metabolites of shikimic acid were synthesised, characterised and tested for genotoxic activity using the Salmonella/mammalian microsome mutagenicity test, the bacterial fluctuation mutagenicity test and the BHK 21 cell transformation test. Under the conditions used, none of these compounds showed any activity. However, shikimic acid itself was active in the BHK 21 cell transformation assay. It therefore seems unlikely that shikimic acid is a carcinogenic initiating agent, but it may act as a carcinogen-promoting agent in the bracken fern (Pteridium aquilinum).

Animals↗
PubMedDate not supplied

Effects of supplemented omega-3 and omega-6 fatty acid rich oils on the cardiovascular system of thermally injured rabbits: changes in plasma and platelet fatty acids.

The effects of omega-3 fatty acid rich oil (MaxEPA oil), omega-6 fatty acid rich oil (soybean oil), and a combination of omega-3 and omega-6 oils (MaxEPA oil + soybean oil) on cardiovascular health-related parameters of thermally injured and control (sham) rabbits were determined. Plasma and platelet analyses of burned rabbits fed with MaxEPA oil revealed significantly higher concentrations of eicosapentaenoic acid and docosahexaenoic acid + myristic acid. Linolenic acid concentrations declined in animals supplemented with soybean oil + MaxEPA oil. At the end of this study the lowest concentrations of linoleic acid and arachidonic acid were found in the sham and burned groups supplemented with soybean oil + MaxEPA oil. Overall, favorable significant differences in plasma and platelet fatty acids concentrations were found in burned or sham groups supplemented with MaxEPA when compared with those of groups supplemented with soybean oil. These favorable changes in plasma and platelet lipids may have an impact on the risk of cardiovascular disease in thermally injured patients.

Animals↗
PubMedDate not supplied

Validation of in vitro and in vivo methods for assessing endocrine disrupting chemicals.

The concepts that require validation in terms of the subject of endocrine disruption are listed and discussed. The main mechanisms by which endocrine disruption can occur are identified, and the assays required for the detection of adverse endocrine disruption toxicities associated with these mechanisms are discussed. The process of assay validation is considered. The validation of structure-activity relationships, the need for reference chemicals, and the problems recently encountered when attempting to reproduce endocrine disruption data are also explored. The most important conclusions derived from this analysis are that given the immature state of research into endocrine disruption toxicity, testing strategies and the types of assay employed should be kept under constant review; inevitably researchers need to accept the fact that future revision of each assay will be required. Second, given the current absence of any chemical that is universally accepted to be devoid of endocrine toxicity, assay specificity will be difficult to assess, and that imposes the need for alternative objective criteria for assessing the value of individual assays.

Animals↗
PubMedDate not supplied

An analysis of hospital productivity and product change.

We developed a model to measure the contribution of changes in length-of-stay, service intensity, and productivity to the unusually low rate of growth in hospital costs per discharge in recent years. From 1992 through 1996 declining length-of-stay explained 97 percent of the decrease in real costs per discharge. Much of the drop was probably caused by care shifted from inpatient to postacute settings. Although complete data for our model are unavailable beyond that point, we cite several "leading indicators" that suggest that length-of-stay declines have played a smaller role in the continued low cost growth of 1997 and 1998 and that productivity may have risen sharply.

Efficiency, Organizational↗
PubMedDate not supplied

Effects of omega-3 and omega-6 fatty acid-rich oils on the cardiovascular system of thermally injured rabbits: changes in plasma triglycerides, plasma cholesterol, relative blood viscosity, platelet count, and bleeding time.

New Zealand white male rabbits were studied to determine how supplements of soybean oil, soybean + MaxEPA oil, or MaxEPA oil affected their cardiovascular status when they were burned. Plasma triglyceride concentrations increased at 2 hours after burn injury (28 days after supplement administration) and declined by the end of the study in all three experimental groups of rabbits. These same animals showed no noticeable differences in the plasma concentrations of total cholesterol or in the high-density lipoprotein cholesterol subfractions. Plasma low-density/very-low-density lipoprotein cholesterol levels remained unchanged at 2 hours after burn injury/sham treatment but increased by the end of the study in all three experimental groups of rabbits. The mean platelet number was significantly higher in burned/sham treated rabbits given soybean oil supplement as compared with numbers in those given either soybean oil + MaxEPA oil or MaxEPA oil supplement. Plasma relative viscosity was highest in the soybean oil-supplemented rabbits, decreased in animals fed soybean oil + MaxEPA, and lowest in MaxEPA oil-supplemented rabbits. Mean bleeding time was lowest in soybean oil-fed rabbits. The bleeding time was higher in rabbits fed soybean oil+MaxEPA oil and highest in MaxEPA oil-supplemented animals. Platelet number and plasma viscosity were highest in the soybean oil-supplemented rabbits and lowest in the MaxEPA oil-supplemented group. The reverse pattern occurred when bleeding time was established. Overall results obtained suggest that supplementation with oils rich in omega-3 and omega-6 fatty acids may have significant effects on the cardiovascular health of burned male New Zealand white rabbits.

Animals↗