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Biomedical subjects

M L Garriott

Publications and source records attributed to M L Garriott.

28 records · Page 2Linked to original sources
PubMed1988

A simplified protocol for the mouse bone marrow micronucleus assay.

Complex and expensive protocols involving multiple sampling times have been proposed and recommended for the in vivo mouse bone marrow micronucleus assay. The purpose of this study was to determine whether a simplified procedure employing two identical exposures and a single sampling time would be equally effective at detecting chemical clastogens. Furthermore, the utility of the protocol was investigated for both intraperitoneal and oral routes of administration. The results obtained from a group of chemicals spanning the known time range for maximum frequency of micronucleus induction prove the effectiveness of this simplified protocol.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

The in vivo effect of 2,6-xylidine on induction of micronuclei in mouse bone marrow cells.

The ability of 2,6-xylidine to produce chromosome breakage and/or spindle malformation in vivo was evaluated by an assessment of the capacity of the compound to induce micronuclei in bone marrow polychromatic erythrocytes. Male ICR mice were administered a single oral dose of 350, 175 or 87.5 mg/kg of 2,6-xylidine by oral gavage and bone marrow was extracted from the femurs 24, 48 and 72 h thereafter. The frequency of micronuclei in animals treated with 2,6-xylidine was not different from that observed for the corresponding solvent treated controls.

Aniline Compounds↗
PubMed1983

AET reduces the frequency of micronuclei in bone marrow cells of mice exposed to gamma radiation.

The purpose of this paper was to determine whether or not a radioprotective agent which binds to DNA and inhibits DNA damage could also provide protection against radiation-induced micronuclei. Male mice were injected intraperitoneally with such an agent, 2-aminoethylisothiouronium bromide hydrobromide (AET), or its solvent 15 min prior to a single 10-min exposure to 60Co gamma rays delivered at various dose rates. Animals were killed 24 hr after irradiation and examined for the frequency of polychromatic erythrocytes containing micronuclei. The results showed a significant dose response to the irradiation for both treatments and a significant reduction in the frequency of micronucleated cells in the mice receiving the radioprotective agent.

Animals↗
PubMed1980

Hyperthermia induced dissociation of the X-Y bivalent in mice.

The mutagenic potential of hyperthermia was examined employing a spermatocyte test on males heat stressed continuously for 2, 3. or 5 days. Stress conditions were 35 +/- 1 degrees C and 65 +/- 3% relative humidity. Males were sacrificed and meiotic preparations made from the testes at various intervals following removal from the stress environment. In this way, chromosome damage could be monitored in all premeiotic and early prophase I stages of spermatogenesis. Results of this study revealed a significant increase in the incidence of X and Y univalents at metaphase I. The significance of this finding is discussed.

Animals↗
PubMedDate not supplied

Genetic toxicology studies with a tumor promoter.

A diuretic antihypertensive agent, SC-33643 (8-[2-ethoxyethyl]-7-phenyl-[1,2,4]triazolo[4,3-c]pyrimidine-5- amine, also known as bemitradine), was tested in the Ames test, in the mouse lymphoma TK +/- mutation assay, in the Chinese hamster ovary cell hypoxanthine guanine phosphoribosyl transferase (CHO/HGPRT) mutation test and in the CHO chromosome aberration assay with and without metabolic activation. Additionally, the compound was tested in the rat primary hepatocyte unscheduled DNA synthesis (UDS) assay and in the mouse bone marrow micronucleus assay. The results were uniformly negative. Contrary to expectations based on the results of the battery of genetic toxicology tests, the compound produced liver, thyroid and mammary tumors in the rat (reported separately). Subsequently, SC-36741 (5-amino-7-phenyl-[1,2,4]triazolo-[1,5-c] pyrimidine-8-ethanol, also known as desethylbemitradine), a major metabolite of SC-33643, was tested in the Ames test, in the CHO/HGPRT mutation test and in the CHO chromosome aberration assay with and without metabolic activation, and was also tested in the rat primary hepatocyte/UDS assay and in the mouse bone marrow micronucleus assay. This metabolite also produced negative results in these tests. Therefore, SC-33643 is a non-genotoxic carcinogen producing tumors in rats without altering DNA or chromosomes.

Animals↗
PubMedDate not supplied

A comparison of the CHO/HGPRT+ and the L5178Y/TK+/- mutation assays using suspension treatment and soft agar cloning: results for 10 chemicals.

The mouse lymphoma assay (MLA) and Chinese hamster ovary (CHO) cell assay are sensitive indicators of mutagenicity. The CHO assay has been modified technically to permit treatment in suspension and soft agar cloning comparable to the MLA. This methodology eliminates the risk of metabolic cooperation and the trauma of trypsinization. In addition, a larger population of cells can be treated and cloned for mutant selection. In order to compare the effectiveness of the test systems, 10 chemicals were evaluated for the induction of forward mutations in the CHO and MLA. Several of these chemicals have been reported as clastogenic; therefore, abbreviated colony sizing was performed to gauge the extent of genetic damage to the MLA cells. Both test systems detected benzo[a]pyrene, mitomycin C, acridine orange, and proflavin, and, with the exception of proflavin, more large colonies were present than small colonies. The suspect clastogen, phenytoin, was not mutagenic in the MLA and produced inconclusive results in the CHO. Ethidium bromide, a clastogen and a bacterial mutagen, was not mutagenic in either the MLA or CHO. Four compounds (p-aminophenol, benzoin, methoxychlor, and pyrene) were positive in the MLA, generally inducing a large number of small colonies, while demonstrating no mutagenic activity in the CHO assay. They have also been shown to be generally nongenotoxic in other test systems. Overall, the modified CHO assay did not appear to be better than the MLA for the detection of mutagenic agents. However, the MLA does appear to have lower specificity.

Agar↗
PubMedDate not supplied

The evaluation of a multiple dosing protocol for the mouse bone-marrow micronucleus assay using benzidine and 2,6-xylidine.

Male ICR mice were treated with 1, 2 or 3 daily doses of either benzidine or 2,6-xylidine. Groups of 5 animals were sacrificed 24 h after the last dose and the bone marrow examined for micronuclei. Benzidine was given at dose levels of 40 and 200 mg/kg and 2,6-xylidine was given at dose levels of 75 and 375 mg/kg. These doses represent 10 and 50% of the respective median lethal doses. Benzidine produced a significant (p less than 0.001) dose related increase in the incidence of micronucleated polychromatic erythrocytes (MPE), while 2,6-xylidine had no effect on the frequency of micronucleated cells. Statistical analyses of the data indicated that the incidence of MPE was independent of the number of doses administered prior to bone marrow harvest.

Aniline Compounds↗
PubMedDate not supplied

Effect of maternal parity on aneuploidy in early mouse embryos.

An attempt to evaluate the incidence of chromosomal aneuploidy in mouse blastocysts recovered from females of various ages and parity levels revealed an insignificant regression coefficient for aneuploidy on age of the female and its square, and an insignificant correlation coefficient for aneuploidy with the number of previous offspring born to the dam. However, significant regression coefficients were obtained for aneuploidy on parity of the dam and its square. These results indicate that not only does aneuploidy increase with parity level, but the rate of increase accelerates as parity level increases. Possible explanations for the increase in aneuploidy and its detrimental effect on reproductive efficiency were discussed.

Aneuploidy↗
PubMedDate not supplied

Investigation of hyperthermia-induced dominant lethal mutations in male mice.

The mutagenic potential of hyperthermia was investigated in a random-bred stock of mice to determine if this is one mechanism by which elevated ambient temperature exerts its deleterious effects on mammalian reproduction. Two dominant lethal assays were conducted to measure mutagenicity during the meiotic and post-meiotic stages of spermatogenesis following various periods of heat stress. Indirect evidence for hyperthermia-induced dominant lethality was obtained in the form of increases in the frequencies of preimplantation loss and sterile matings. However, the large number of sterile matings precluded unambiguous statistical analysis of the incidence of early embryonic mortality that would have provided direct evidence of induced dominant lethality. Control data indicated that the stock of mice used in this experiment is an excellent choice for dominant lethal studies because of the large number of implants and the low frequency of embryonic mortality.

Analysis of Variance↗