Cytotoxicity and mutagenicity of coal oils in the CHO/HGPRT assay. 1984

D M DeMarini, and P A Brimer, and A W Hsie

We used the Chinese hamster ovary cell/hypoxanthine-guanine phosphoribosyl-transferase (CHO/HGPRT) assay to determine the cytotoxicity and mutagenicity of a crude coal oil, the neutral fraction of this crude, and the following three subfractions of the neutral fraction: aliphatic, neutral polar, and a subfraction composed of polycyclic aromatic hydrocarbons plus neutral nitrogen heterocyclics. We also studied the cytotoxicity and mutagenicity of a blend of light and heavy coal-derived fuel oils before and after hydrogenation. All seven mixtures were highly cytotoxic to CHO cells, but the addition of S9 reduced the cytotoxicity. Also, hydrogenation reduced the cytotoxicity of the blend of coal-derived fuel oils. Although highly cytotoxic, none of the seven mixtures induced a clear mutagenic response in the CHO/HGPRT assay. However, previous work has shown that all of the mixtures except the aliphatic subfraction and the blend after hydrogenation are mutagenic in the histidine-reversion assay in Salmonella typhimurium. Based on chemical analyses of the mixtures, the differential sensitivity of Salmonella and CHO cells to nonmutagenic cytotoxins, and studies of the neutral fraction to which additional benzo[a]pyrene had been added, we conclude that the disparity between the results in Salmonella and those obtained in the CHO/HGPRT assay is probably due to the much greater sensitivity of CHO cells (relative to Salmonella) to the cytotoxins in these coal oils. This sensitivity, coupled with the low concentrations of mutagens relative to nonmutagenic cytotoxins in the coal oils, prevents exposure of the cells to concentrations of the mutagens in the mixtures that are high enough to be quantified in the CHO/HGPRT assay.

UI MeSH Term Description Entries
D007041 Hypoxanthine Phosphoribosyltransferase An enzyme that catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate and hypoxanthine, guanine, or MERCAPTOPURINE to the corresponding 5'-mononucleotides and pyrophosphate. The enzyme is important in purine biosynthesis as well as central nervous system functions. Complete lack of enzyme activity is associated with the LESCH-NYHAN SYNDROME, while partial deficiency results in overproduction of uric acid. EC 2.4.2.8. Guanine Phosphoribosyltransferase,HPRT,Hypoxanthine-Guanine Phosphoribosyltransferase,IMP Pyrophosphorylase,HGPRT,HPRTase,Hypoxanthine Guanine Phosphoribosyltransferase,Phosphoribosyltransferase, Guanine,Phosphoribosyltransferase, Hypoxanthine,Phosphoribosyltransferase, Hypoxanthine-Guanine,Pyrophosphorylase, IMP
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D009152 Mutagenicity Tests Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests. Genetic Toxicity Tests,Genotoxicity Tests,Mutagen Screening,Tests, Genetic Toxicity,Toxicity Tests, Genetic,Genetic Toxicity Test,Genotoxicity Test,Mutagen Screenings,Mutagenicity Test,Screening, Mutagen,Screenings, Mutagen,Test, Genotoxicity,Tests, Genotoxicity,Toxicity Test, Genetic
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D010053 Ovary The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE. Ovaries
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002999 Clone Cells A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed) Clones,Cell, Clone,Cells, Clone,Clone,Clone Cell
D003033 Coal Tar A by-product of the destructive distillation of coal used as a topical antieczematic. It is an antipruritic and keratoplastic agent used also in the treatment of psoriasis and other skin conditions. Occupational exposure to soots, tars, and certain mineral oils is known to be carcinogenic according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985) (Merck Index, 11th ed). Clinitar,Estar,Tar, Coal

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