Toxic and mutagenic effects of carcinogens on the mitochondria of Saccharomyces cerevisiae

Egilsson, Valgarður; Evans, Ivor H.; Wilkie, D.

doi:10.1007/bf00433303

Cited by 77 publications

(19 citation statements)

References 38 publications

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“…Benzene failed to induce petites and gene conversion/crossing over in yeast (55,56); however, it did induce aneuploidy in yeast (57). Benzene was negative for somatic mutation in Drosophila melanogaster in an early study by Nylander et al (58); however, it was positive in the wing-spot assay (59).…”

Section: Nonmammalian Eukaryotic Systemsmentioning

confidence: 99%

Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice.

Huff

Haseman

DeMarini

et al. 1989

Environ Health Perspect

113

107

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Toxicology and carcinogenesis studies of benzene (CAS No. 71-43-2; greater than 99.7% pure) were conducted in groups of 60 F344/N rats and 60 B6C3FW mice of each sex for each of three exposure doses and vehicle controls. These composite studies on benzene were designed and conducted because of large production volume and widespread human exposure, because of the epidemiologic association with leukemia, and because previ. ous experiments were considered inadequate or inconclusive for determining carcinogenicity in laboratory animals. Using the results from 17-week studies, doses for the 2-year studies were selected based on clinical observations (tremors in higher dosed mice), on clinical pathologic findings (lymphoid depletion in rats and leukopenia in mice), and on body weight effects. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten animals in each of the 16 groups were killed at 12 months, and necropsies were performed. Hematologic profiles were performed at 3-month intervals.For the 2-year studies, mean body weights of the top dose groups of male rats and of both sexes of mice were lower than those of the controls. Survivals of the top dose group of rats and mice of each sex were reduced; however, at week 92 for rats and week 91 for mice, survival was greater than 60% in all groups; most of the dosed animals that died before week 103 had neoplasia. Compound-related nonneoplastic or neoplastic effects on the hematopoietic system, Zymbal gland, forestomach, and adrenal gland were found both for rats and mice. Further, the oral cavity was affected in rats, and the lung, liver, Harderian gland, preputial gland, ovary, and mammary gland were affected in mice. Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenicity of benzene in male F344/N rats, female F344/N rats, male B6C3FW mice, and female B6C3FM mice. In male rats, benzene caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas and squamous cell carcinomas of the oral cavity, and squamous cell papillomas and squamous cell carcinomas of the skin. In female rats, benzene caused increased incidences of Zymbal gland carcinomas and squamous cell papillomas and squamous cell carcinomas of the oral cavity. In male mice, benzene caused increased incidences of Zymbal gland squamous cell carcinomas, malignant lymphomas, alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas or carcinomas (combined), Harderian gland adenomas, and squamous cell carcinomas of the preputial gland. In female mice, benzene caused increased incidences of malignant lymphomas, ovarian granulosa cell tumors, ovarian benign mixed tumors, carcinomas and careinosarcomas of the mammary gland, alveolar/bronchiolar adenomas, alveolar/bronchiolar carcinomas, and Zymbal gland squamous cell carcin...

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Section: Nonmammalian Eukaryotic Systemsmentioning

confidence: 99%

Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice.

Huff

Haseman

DeMarini

et al. 1989

Environ Health Perspect

113

107

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“…Why the mitochondrion should be the primary target is not clear but it may be due to organizational differences between mitochondrial DNA and nuclear DNA -the former is a circular molecule and is not complexed with packaging proteins as is nuclear DNA. There are other features of mitochondria which may make them more vulnerable to toxic agents and these are discussed by Egilsson et al (1979). Many drugs used in cancer chemotherapy besides MGBG may have primary antimitochondrial activity.…”

Section: Discussionmentioning

confidence: 99%

Primary Antimitochondrial Activity of the Cancer Drug Methylglyoxal Bis(guanylhydrazone) in Yeast Cells

Diala¹,

Evans²,

Wilkie³

1980

Microbiology

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Primary action of methylglyoxal bis(guanylhydrazone) (MGBG) on the yeast mitochondrial system was demonstrated by (1) selective inhibition of cell growth in non-fermentable medium, (2) blockage of mitochondrial synthesis of cytochromes aa3 and b and (3) ultrastructural aberration. The drug caused extensive deletions in mitochondrial DNA detected by an increase in the frequency of the mitochondrial mutant petite but had little or no effect on cell viability. Growth inhibition by MGBG had any effect on growth inhibition by ethidium bromide. Strains showed no cross-correlation in their tolerance to MGBG and ethidium bromide.

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“…Yeast mitochondria, in addition to controlling energy metabolism and synthesis of selected polypeptides, also exert control on the biogenesis of the cell-surface complex in yeast (Linstead et al, 1974;Evans and Wilkie, 1976a,b;Mahler and Wilkie, 1978;Egilsson et al, 1979). Thus, the petite mutation affects agglutinability, flocculation, tolerance to drugs, utilization of sugars, and also the plasma membrane proteins of yeast cells (Wilkie and Nudd, 1981 ;Wilkie and Evans, 1982).…”

Section: F M I T O C H O N D R I a L F U N C T I O N Smentioning

confidence: 99%

Lipids in the Structure and Function of Yeast Membrane

Prasad

1985

Advances in Lipid Research

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Toxic and mutagenic effects of carcinogens on the mitochondria of Saccharomyces cerevisiae

Cited by 77 publications

References 38 publications

Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice.

Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice.

Primary Antimitochondrial Activity of the Cancer Drug Methylglyoxal Bis(guanylhydrazone) in Yeast Cells

Lipids in the Structure and Function of Yeast Membrane

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