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Biomedical subjects

C R Richardson

Publications and source records attributed to C R Richardson.

At least 37 records · Page 2Linked to original sources

Activity of bromochlorodifluoromethane (BCF) in three mutation tests.

The halocarbon BCF was tested in 3 assays to assess its mutagenicity and clastogenicity. It produced a positive response in Salmonella typhimurium strain TA1535 but was negative in TA1537, TA1538, TA98 and TA100. In an L5178Y mouse lymphoma microwell assay (TK locus), BCF was negative. BCF was administered at 5000 and 50 000 ppm in air for 6 h to groups of C57B1/6J mice of both sexes. Animals were killed at 24, 48 and 72 h after cessation of exposure and the incidence of bone marrow micronuclei per 1000 PCEs determined. There was no significant difference in the incidences of micronuclei between untreated animals and those exposed to either concentration of BCF at any of the sampling times. These results suggest that BCF is mutagenic in vitro in only one strain of Salmonella; in mammalian cells the compound induced no gene mutation in vitro nor clastogenic activity in vivo at doses that also produced clear evidence of toxicity.

Animals↗

Feedlot performance and carcass characteristics of steers fed diets containing ammonium salts of the branched-chain fatty acids and valeric acid.

Two trials were conducted to study the effects of feeding a mixture of ammonium salts of isovaleric, 2-methylbutyric, isobutyric and valeric acids (AS-VFA) on feedlot performance and carcass characteristics of growing and finishing Angus, Hereford and Angus X Hereford steers. In trial 1,192 steers (8 steers/pen, 6 pen/treatment) averaging 251 kg body weight and in trial 2, 240 steers (8 steer/pen, 7 pens/treatment, 9 pens/control treatment) averaging 216 kg body weight were randomly assigned to four anhydrous ammonium salt-volatile fatty acid (AS-VFA) treatment levels: 0 (control), .14, .28 and .42% of the diet dry matter (DM). In each trial, the growing and finishing diets were isocaloric, isonitrogenous and supplemented with monensin (26 mg/kg diet). In both trials, steers received implants of 200 mg progesterone and 20 mg estradiol benzoate. Combined data from the trials confirmed the absence of average daily gain and feed conversion responses during the growing period. During the finishing period, the combined data for gain and feed conversion for the control steers and the steers fed .14, .28 and .42% AS-VFA were 1.43, 7.09; 1.43, 6.99; 1.48, 6.67 and 1.45, 6.80, respectively. Gains increased 3.5% (P less than .10) and feed conversion improved 5.9% (P less than .07) in steers fed .28% AS-VFA compared with gain and feed conversion of the control steers. At the end of the growing period in the first trial, a urea dilution technique was used to estimate the body composition of 12 steers from each treatment. Estimates of percent body fat and percent body protein were similar (P greater than .20) for all steers, irrespective of treatment. At the end of the trials, carcass yield grades for the combined data were 2.6 and 2.8 (P less than .10) for steers fed .28% AS-VFA and for the control steers, respectively. Carcass weight, dressing percentage and marbling score were lower (P less than .10) in steers fed AS-VFA than for steers fed the control. However, in general, carcass characteristics were not greatly influenced by AS-VFA. A possible use for a supplement containing branched-chain fatty acids and valeric acid in finishing steer diets is suggested by the improvement in feedlot performance and by the slight increase in carcass yield.

Animals↗

Cytogenetic effects of benzene: dosimetric studies on rats exposed to benzene vapour.

Rats were exposed to benzene vapour at nominal concentrations in air of 1, 10, 100 and 1000 ppm acutely for 6 h. Bone marrow cells from each animal were examined for chromosomal abnormalities 24 h after the end of the exposure period. This analysis was carried out on 250 metaphases per animal where possible and showed a significant increase in the percentage of cells with chromosomal abnormalities, excluding gaps, in the groups of animals exposed to 100 and 1000 ppm benzene. In the 10-ppm and 1-ppm exposure groups there were elevated levels of cells with abnormalities which showed evidence of being dose-related, although they were not statistically significant.

Animals↗

The human lymphocyte in vitro cytogenetic assay: positive and negative control observations on approximately 30000 cells.

Data are presented from the cytogenetic analysis of the peripheral lymphocytes from 94 male and 15 female donors. However, a much smaller number of regular donors were selected for regular use. A total of 28674 cells were analysed and these acted as negative and positive controls in the in vitro human lymphocyte tests accumulated in this laboratory over a 6-year period. The significant observations were:. (1) in untreated and solvent control treated cultures (a) no chromosomal interchanges were observed in 21570 cells; (b) the incidence of dicentrics was less than 1 per 10000 cells; (c) other types of aberrations were seen with an increased frequency, chromosomal gaps being the most variable. (2) The reference clastogens mitomycin C and cyclophosphamide produced high and remarkably consistent yields of all types of aberrations. It is concluded that when screening compounds in vitro for new genotoxins, aberrations such as chromosomal interchanges and dicentrics (due to their rarity in negative control cultures) should be accorded greater significance than the several other types of aberrations routinely seen. These conclusions emphasize the value of maintaining and updating adequate historical control records.

Antibiotics, Antineoplastic↗

Evaluation of some formaldehyde-release compounds and other biocides in the mouse micronucleus test.

A number of biocidal chemicals were tested for clastogenic activity in the micronucleus test using C57Bl/6J mice. The materials tested were: 5-chloro-2-methyl-4-isothiazolin-3-one (I), N-methyl-isothiazolone hydrochloride (II), Glokill 77 and Parmetol A23. Two of the biocides (Glokill and Parmetol) depend on the release of formaldehyde for their activity while the other two compounds are the active chemicals in the biocide Kathon. Hexamethylphosphoramide (HMPA) was tested as the positive control for the series and N,N-dinitrosopentamethylenetetramine (DNPT) as the negative control. HMPA produced significant dose-related increases in the incidence of micronuclei whereas DNPT, I, II, Glokill and Parmetol A23 were without effect.

Animals↗

Activity of vinyl chloride monomer in the mouse micronucleus assay.

C57Bl/6J mice of both sexes were exposed to 50 000 ppm vinyl chloride monomer (VCM) for 6 h. Animals were killed 24 and 48 h after cessation of exposure and examined for the presence of micronuclei in bone marrow cells. At 24 h the control incidences of micronuclei per 1000 polychromatic erythrocytes (PCEs) were 2.6 (male) and 1.2 (female), while in animals exposed to VCM the incidences were 24.6 (male) and 25.0 (female). At 48 h the control incidences were 2.2 (male) and 1.6 (female) and in the VCM exposed animals 7.2 (male) and 4.4 (female).

Animals↗

A comparison of the incidence of micronuclei in blood and bone marrow in 3 strains of mouse dosed with cyclophosphamide or hexamethylphosphoramide (HMPA).

The response of 3 strains of mouse (C57Bl/6J, C3H/C57 hybrid and BALBC/CBA) to cyclophosphamide (75 mg/kg) and hexamethylphosphoramide (HMPA) (1.28 ml/kg) were compared in the micronucleus test. Each compound was administered by intraperitoneal injection on two consecutive days and samples of bone marrow and blood taken for examination at 48 and 72 h after the first injection. Both test chemicals produced a statistically significant increase (P 0.001) in the incidence of micronuclei in bone marrow cells in all strains at both sampling times but the response with HMPA in C57Bl/6J mice appears to occur earlier than in the other two strains. Significant increases in micronuclei were seen in circulating erythrocytes only at 48 h in C57Bl/6J mice with both test chemicals and in C3H/C57 mice only with cyclophosphamide.

Animals↗

Chromosomal analysis in vinyl chloride exposed workers: comparison of the standard technique with the sister-chromatid exchange technique.

A group of 21 workers occupationally exposed to vinyl chloride and 6 controls were examined for the presence of chromosomal aberrations or sister-chromatid exchanges in their peripheral lymphocytes. These people comprised a second sampling from a group of exposed workers and controls first examined 18 months earlier. The vinyl chloride exposed workers showed levels of chromosomal aberrations elevated above those of the controls, but there was only a slight increase in sister-chromatid exchanges (per cell or per chromosome) and this increase was not statistically significant. Sister-chromatid exchanges (SCEs) were also examined from in vitro cultures of lymphocytes exposed in G0/early G1 and late G1/early S phase to vinyl chloride, both with and without metabolic activation. There was no increase in SCEs in vitro without metabolic activation but there was a marked increase with metabolic activation and this increase was shown to be independent of cell-cycle phase. It thus was apparent that the small increases of SCEs in workers were not due to the inability of vinyl chloride to induce SCEs in human lymphocytes but were probably because of low exposures and SCE levels could have returned to normal relatively quickly after exposure. The present study suggested that the analysis of longer-living conventional chromosomal aberrations appeared to be a more sensitive monitor of exposure to vinyl chloride in exposed workers than the estimation of SCEs; however, it should be noted that in a 3rd sampling taken 24 months later the exposed workers had chromosomal aberration levels similar to the controls.

Cells, Cultured↗

Issues relevant to the assessment of chemically induced chromosome damage in vivo and their relationship to chemical mutagenesis.

Rats have been exposed by different routes of administration (inhalation, orally and intraperitoneally) to known mutagens and their bone-marrow cells sampled at different times to determine the extent of chromosome damage. The mutagens investigated were ethyl methanesulphonate, mitomycin C, trimethylphosphate, benzene and vinyl chloride, at single and/or multiple doses (5 consecutive daily). Various categories of chromosome damage were observed in all cases. However, the extent of damage due to chromosome and chromatid gaps was greater than, and generally increased in parallel with, other categories of damage. It has been suggested tht chromosome and chromatid gaps are indicative of toxic phenomena but this study suggests that such aberrations could be useful and sensitive indicators of chemically induced genetic damage. In addition the study has also confirmed that single exposure is as effective as multiple exposure in producing chromosome damage and that the correct sampling time is necessary to detect this damage. Therefore for screening purposes a time course sampling after a single treatment regime would be suitable for detecting the mutagenic potential of a chemical.

Animals↗

The genotoxic potential of bases and nucleosides.

This study was conducted to determine if naturally occurring cell constituents could themselves cause mutation. All the bases and their corresponding nucleosides have been shown to produce chromosome damage in P338 mouse lymphoma and Chinese hamster ovary cells in culture. In addition thymidine has produced an increase in V79 cells resistant to 8-azaguanine and ouabain. Such damage probably arises as a result of imbalanced DNA-precursor pools. Thus mutagenic events may arise by mechanisms unrelated to direct alterations to DNA.

Animals↗

Chromosomal analyses in vinyl chloride exposed workers. Results from analysis 18 and 42 months after an initial sampling.

In a previous study (Purchase et al., Mutation Res., 57 (1978) 325-334) it was reported that 57 workers occupationally exposed to vinyl chloride had an increase in the incidence of chromosomal abnormalities in their lymphocytes by comparison with 24 control workers. Since that time (July 1974) threshold limit values for vinyl chloride and plant exposure levels have been reduced. In the present study, 2 further samples from the same population of workers have been analysed for chromosomal aberrations 18 and 42 months after the initial sampling. At 18 months, 21 VC workers and 6 on-site controls were investigated as were 23 workers and 8 on-site controls at 42 months. In the second sampling there was a tendency to an increase in chromosomal abnormalities of VC-exposed workers except in those people who had changed occupation. By the third sampling, however, there was a decrease by comparison with previous samplings and the levels of abnormalities had returned to values similar to those of the controls. Thus, reduction in exposure to vinyl chloride is accompanied by a reduction in the chromosomal abnormalities to levels indistinguishabe from those of controls.

Adult↗

Cancer of the endometrium---a multiparametric study.

Haematological and immunological studies were performed on 36 patients with carcinoma of the endometrium prior to treatment. Haematological and coagulation studies, excluding fibrinogen, showed only minimal abnormality. However, tests for acute phase reactant proteins were abnormal in the majority of patients. There was a reduction in T cells in 31% of patients and a reduction in stimulation with PHA and PWM in 84 and 42% of patients, respectively. Autoantibodies to normal tissue antigens were present in half the patients and immune complexes were increased in 45% of patients. Carcinoembryonic antigen and B(2)-microglobulin were increased in 27 and 47% of patients respectively. Although specific tests for endometrial cancer are not yet available, a profile of tests might be of value in the diagnosis and follow-up of patients with the condition.

Antigens, Neoplasm↗

Digestibility of chemically treated cotton plant byproduct and effect on mineral balance, urine volume and pH.

Effects of chemical treatment of cotton byproduct (CBP) on apparent digestibility, mineral balance, urine volume and pH and in vitro digestibility were studied in three experiments with growing lambs and a rumen-fistulated steer. Apparent dry matter digestibility (DMD) and apparent organic matter digestibility (OMD) of total diets were increased (P < .01) by 35.4 and 35.7% in Exp. 1, and by 16.2 and 13.6% in Exp. 3. The CBP was treated wih 4% (4 kg sodium hydroxide/96 kg CBP dry matter) sodium hydroxide (NaOH) and fed at 70% of the total dietary intake. Treatment of CBP with nitric and sulfuric acid increased (P < .01) both DMD and OMD 25% (Exp. 1). In Exp. 2, NaOH treatment decreased (P < .05) organic matter, cellulose and lignin content of CBP and increased (P < .05) ash content. In vitro digestibilities of dry matter, organic matter and cell walls were increased (P < .05) by NaOH treatment. Volume of urine excreted by lambs in Exp. 1 and 3 was increased (P < .05) 53% but urine pH was affected by NaOH treatment. Acid treatment, however, resulted in a decrease (P < .01) in urine pH (9.4 vs 5.3). Feeding NaOH-treated CBP at increasing percentages of the diet increased Na balance and decreased K, Cl and Mg balance. NaOH-treated CBP had no effect on Ca or P balance. These results indicate the NaOH treatment of cotton byproduct increases apparent digestibility and that consumption of the treated product may increase the animal's requirement of K, Cl and Mg. Furthermore, urine volume is increased but urine pH is not affected by NaOH treatment.

Animal Feed↗

Chromosomal analyses in vinyl chloride-exposed workers.

Chromosomal morphology from cultured peripheral lymphocytes was studied in 81 men; 57 of the men were employed on plants manufacturing vinyl chloride or polyvinylchloride, 19 were on-site controls and 5 were off-site controls. There was a significant increase in chromosomal abnormalities in the exposed workers when compared with the controls. The greatest statistically significant increase in total B and total C cells occurred in autoclave operators, with smaller increases in other job categories. The increase in chromosomal aberrations was correlated with the length of exposure and with a history during the year prior to sampling (1973--1974) of exposure to excursion levels of vinyl chloride. Information on smoking habits was obtained 18 months after blood sampling and a positive correlation between these and total C cell abnormalities was found. There was no positive correlation with various other parameters (bilirubin, platelets, gamma-glutamyltranspeptidase, alkaline phosphatase, alanine transaminase and aspartate transaminase). It was not possible to estimate which of the three parameters (smoking history, length of employment or exposure to excursion levels) was the most important.

Chromosomes↗

An assessment of the clastogenic potential of 4-chloromethylbiphenyl in human lymphocytes in vitro.

The clastogenic potential of 4CMB was assessed in vitro in human lymphocytes from 4 donors (2 male and 2 female) both with and without auxiliary metabolic activation. Although there were some variation in the response of the cells from different donors to 4CMB using 2 criteria for interpretation of the results; it was concluded that 4CMB was a clastogen, but only at dose levels that caused some cytotoxicity. The response was amplified by the inclusion of chromatid and chromosome gaps in the analysis of chromosome damage.

Biphenyl Compounds↗