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Biomedical subjects

J C Ball

Publications and source records attributed to J C Ball.

At least 19 recordsLinked to original sources

Detection of oxidative mutagens in an urban air-particulate extract: a preliminary study.

The Ames assays strains TA98 and TA100 have been useful in characterizing complex mixtures from organic solvent extracts of particles from diesel-powered vehicles, ambient air, and other sources. In this paper we report preliminary experiments using TA102, a bacterial strain that detects compounds that can oxidize DNA, to characterize the mutagenicity of an ambient air sample collected in Ann Arbor, MI. Four sets of ambient air filters were collected in duplicate over a period of several days. The mutagenicities of methylene chloride extracts of these filters were compared using strains TA98, TA100 and TA102. The concentration-mutagenicity data for TA98 and TA100 were linear over the concentration range 0-200 micrograms extract/plate. The mutagenicity of the extracts using TA102 was much lower than the other two strains and was non-linear over the concentration range tested. These results suggest that it would be difficult to use TA102 to identify the oxidative mutagens present in an ambient air particulate extract.

Air Pollutants

Solvent extraction efficiencies of mutagenic components from diesel particles.

In order to determine the efficiency of organic solvent extractions of fresh diesel-engine exhaust particles a series of Soxhlet extractions were set up using single and sequential extractions of fresh diesel particles with solvents of increasing polarities. Single extractions were carried out with methylene chloride, methanol, acetone and acetonitrile. A single filter was sequentially extracted with methylene chloride followed by methanol, acetone and acetonitrile. Methylene chloride extracted the most mutagenicity relative to the other three solvents. In addition, methylene chloride extracted 97% of the total extracted mutagenicity from a sequential series of extractions. Therefore, we conclude that of the solvents tested methylene chloride extracts the highest proportion of mutagens from fresh diesel exhaust and little mutagenicity is lost using methylene chloride as the only extraction solvent.

Acetone

Ames assay mutagenicity and electronic structure calculations of bromomethylfluoranthenes, chloromethylfluoranthenes, and hydroxymethylfluoranthenes.

The mutagenicities of the five possible isomers of bromomethylfluoranthene, chloromethylfluoranthene, and hydroxymethylfluoranthene were determined in the Ames assay using strains TA100 and TA98 without the addition of rat-liver S9 tissue extract. The mutagenicities of the bromomethyl and chloromethylfluoranthenes ranged from 25 to 6000 rev./nmol. The most mutagenic compound was 8-chloromethylfluoranthene in strain TA98 (6000 rev./nmol). The reactivities of the bromomethylfluoranthenes and the chloromethylfluoranthenes were estimated from electronic structure calculations using the MNDO and the PM3 semi-empirical methods. The bromomethylfluoranthenes showed the smallest differences between the heats of formation of the carbocations and the heats of formation of the parent bromomethyl derivatives. Therefore, the bromomethylfluoranthenes were estimated to be the most reactive of the halomethylfluoranthenes studied. The compound that showed the largest change in heat of formation (the most stable halomethylfluoranthene) going from the halomethylfluoranthene to the carbocation was 2-chloromethylfluoranthene. However, neither the most reactive nor the most stable halomethylfluoranthenes were the most mutagenic in either strain of bacteria. These results are interpreted to suggest that the reactivity of the parent halomethylfluoranthene is not a critical factor in the mechanism by which these compounds are mutagenic, but some other factor, perhaps intercalation, must be a critical step in the mechanism of mutagenesis of these compounds.

Acetone

A treatment crisis: cocaine use by clients in methadone maintenance programs.

We surveyed 11 methadone maintenance treatment programs in the Baltimore, Maryland, area to examine cocaine use among their 2414 clients and the methods employed to cope with that use. The percent of clients with at least one urine sample positive for cocaine during the month previous to study was 15.7% (379/2414) and ranged from 5.9% to 33.0% among the 11 programs. We determined the programs' use of monitoring strategies, treatment services, and administrative controls. We discuss the policy implications of our findings for methadone maintenance programs' efforts to address cocaine use with particular regard to the epidemic of human immunodeficiency virus (HIV) among intravenous drug users, their sexual partners, and offspring.

Baltimore

Mutagenicity and induction of sister chromatid exchange by optically active enantiomers of secondary butyl methanesulfonate.

This report describes experiments in which a chiral alkyl methanesulfonate was used to investigate possible mechanisms by which alkylating agents cause their mutagenic, cytotoxic, and clastogenic effects. Optically active enantiomers and the racemic mixture of 2-butyl methanesulfonate (2-BMS) were cytotoxic and mutagenic in Chinese hamster V79 cells and in AS52 cells and mutagenic in Salmonella typhimurium strains TA100 and TA1535 (without the addition of exogenous metabolizing systems). Within the experimental uncertainties, the cytotoxicity and mutagenicity curves were the same for the R and S enantiomers and for the racemic mixture. The 2-BMS isomers were cytotoxic and induced sister chromatid exchanges (SCE) in CHO-K1-BH4 cells. The cytotoxicity curve was similar to that observed with V79 and AS52 cells. The induction of SCE was linear between 1 and 6 mM 2-BMS with no differences discernable between the isomers. The results can be interpreted two ways. The first interpretation is that 2-BMS reacts via a carbocation, and the second interpretation involves an SN2 reaction of 2-BMS with DNA. The latter interpretation suggests that the mechanisms of mutagenesis, cytotoxicity, or the induction of SCE cannot distinguish between small (four-carbon) optically active DNA adducts. We favor the second interpretation because of solvolysis experiments showing the complete inversion of configuration of optically active 2-octyl methanesulfonate (2-OMS, Weiner and Sneen: J American Chemical Society 87:287-291, 1965). While we assume that optically active 2-BMS will react using the same mechanism as chiral 2-OMS, we cannot exclude the possibility that 2-BMS reacts via a carbocation intermediate.

Animals

The Lexington addicts, 1971-1972: demographic characteristics, drug use patterns, and selected infectious disease experience.

The demographics, drug habits, and medical complications of a cohort of 1,129 addicts treated at Lexington in the period 1971-1972 were studied. These patients, admitted from 41 different states, had a mean period of addiction of 5.4 years. Over one-third of the sample had engaged in pimping or prostitution, and there were no differences by gender in terms of involvement. Eight-eight percent had shared injection equipment, and surprisingly, 78% admitted to some effort at sterilizing their "works." Hepatitis was the most common associated medical condition: 87% had serologic markers of hepatitis B virus (HBV) infection, 60% had evidence of hepatitis A virus (HAV) exposure, and 47% had abnormal liver function parameters. Gynecomastia was evident in 2% of male subjects. Thirteen percent of the sample had a reactive VDRL assay, but 64% of these were biologically false positive. Subtle abnormalities of immune function were also observed; 18% of the patients had recent unexplained weight loss, 6% had lymphadenopathy, 8% had leukopenia, and 2% had lymphocytopenia. We conclude that both HBV and HAV were important infectious disease risks in these addicts, and that many evidenced deficiencies in immune function well before AIDS became a major public health concern.

Adolescent