Recombinogenicity and mutagenicity of saccharin in Saccharomyces cerevisiae

When the essential and distinctive cell walls of either pathogenic or nonpathogenic fungi break, cytoplasmic membranes rupture and fungi die. This fungicidal activity was discovered previously on nonproliferating Saccharomyces cerevisiae cells treated briefly with the oxidative tool and anticancer drug family of bleomycins. The present studies investigated effects of bleomycin on growing fungal organisms. These included the medically important Aspergillus fumigatus and Cryptococcus neoformans, as well as the emerging human pathogen and fungal model, S. cerevisiae. Bleomycin had its highest potency against A. fumigatus. Scanning electron microscopy and thin-section transmission electron microscopy were used to study morphological growth characteristics. Killing and growth inhibition were also measured. Long, thin, and segmented hyphae were observed when A. fumigatus was grown without bleomycin but were never observed when the mold was grown with the drug. Bleomycin arrested conidial germination, hyphal development, and the progression and completion of cell wall septation. Similarly, the drug inhibited the construction of yeast cell wall septa, preventing cytokinesis and progression in the cell division cycle of S. cerevisiae. Even when cytoplasms of mother and daughter cells separated, septation and cell division did not necessarily occur. Bizarre cell configurations, abnormally thickened cell walls at mother-daughter necks, abnormal polarized growth, large undivided cells, fragmented cells, and empty cell ghosts were also produced. This is the first report of a fungicidal agent that arrests fungal growth and development, septum formation, and cytokinesis and that also preferentially localizes to cell walls and alters isolated cell walls as well as intact cell walls on nongrowing cells.The unique cell wall that surrounds fungal cells is absolutely essential for their survival. The cell wall of pathogenic fungi has evolved for survival from environmental factors and host defenses (7,16,18,21,60). The ability of cell walls to evade such factors contributes to the power of pathogenic fungi to cause a wide spectrum of clinical disease (45). Moreover, the unique arrangement of the molecular species forming the structure of the fungal cell wall makes it an excellent target for drug intervention (3,6,24,44,46,54). Thus, the elucidation of the mechanisms of action of agents that interact with the molecules forming the cell walls will yield new insights into fungal cell wall structure, formation of cell walls between dividing cells, and cell division. For fungal pathogens, an understanding of the mechanisms of action of cell wall-specific agents should assist in the design of wall-specific antifungal drugs.Saccharomyces cerevisiae has long been a unicellular fungal model for studies of basic mechanisms. Since this budding yeast is also an emerging opportunistic human pathogen (15,38,42) with properties frequently observed in pathogenic fungi (4,29,30), the yeast is also developing as a model fungal pathogen (12). The dis...

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“…S. cerevisiae strain CM1069-40 (37) was inoculated at 5 ϫ 10 3 or 5 ϫ 10 5 cells per ml into nonsynthetic complete growth medium (YPAD [31]). …”

Section: Fungal Strains and Culturing Conditions A Fumigatus (Isolamentioning

confidence: 99%

Fungal Cell Wall Septation and Cytokinesis Are Inhibited by Bleomycins

Moore

McKoy

Valle

et al. 2003

Antimicrob Agents Chemother

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“…In the presence of S. cerevisiae saccharin was found to inhibit the sporulation process and slightly increase the occurrence of diploid and disomic meiotic products without affecting the frequency of recombination (Persic, 1986). At a concentrations of 2-20 mg/mL, sodium saccharinate did not significantly affect cell growth, but slightly reduced cells survival; cell survival decreased even more at a concentration of 100 mg/mL (Moore et al, 1979).…”

Section: Literature Studies On the Bioactivity Of Saccharin And Its D...mentioning

confidence: 81%

Pelvic Osteotomies in Children and Adults - Experience of University Medical Centre Ljubljana

Kovačić¹,

Zore²,

Stražar³

2022

Socratic Lectures 7

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Nowadays, hip dysplasia is recognized and treated mainly conservatively due to good screening program and early detection. There are still some cases found after first year of life, in later childhood and in adults. These cases are treated with pelvic osteotomies to improve femoral head coverage and joint stability and to decrease the hip stress with the final goal to preserve the joint in longer term. There are three subtypes of pelvic osteotomies. The ones pertaining to first type are redirectional osteotomies, which are incomplete osteotomies with the aim to reduce overall volume and redirect the acetabulum by a hinge located between triradiate cartilage and pubic symphysis. This type in-cludes Salter, Pemberton, Dega and San Diego osteotomies. The osteotomies pertaining to the second type are reorientational osteotomies, which are complete osteotomies with the aim to reorient the whole acetabulum. This type includes periacetabular and triple osteotomies. The osteotomies per-taining to the third type are salvage osteotomies which enlarge the acetabulum and medialise the hip center in arhritic and/or incongruent joint and are performed in hips in which the reorientational osteotomy is contraindicated. This type includes shelf and Chiari osteotomies. In University Medical Centre Ljubljana, most of the above-mentioned osteotomies are being performed, however, yearly numbers are small. Redirectional osteotomies have been performed for many years in the Pediatric orthopaedic department and yearly number is under 10 cases. Reorientational osteotomies on young adults are made through minimally invasive approach for periacetabular osteotomy described by Soebbale at al. (2015). In selected cases, electromagnetic surgical navigation system is used for more precise positioning of the acetabular fragment. Keywords: Hip dysplasia, pelvic osteotomy, periacetabular osteotomy, hip preservation, hip pain

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“…With FANFT, however, administration of an initiating dose requires 4 to 6 weeks of the chemical in the diet at a level of 0.2% (18). In vitro assays involving Saccharomyces have indicated that sodium saccharin is able to cause these genetic changes (47). The urinary bladder normally has a very low rate of cell turnover; the labeling index is approximately 4 per 10,000 epithelial cells (35).…”

Section: Cell Proliferation and Bladder Carcinogenesismentioning

confidence: 99%

Promotion in Urinary Bladder Carcinogenesis

Cohen¹

1983

Environmental Health Perspectives

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JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. The National Institute of Environmental Health Sciences (NIEHS) and Brogan & Partners are collaborating with JSTOR to digitize, preserve and extend access to Environmental Health Perspectives.Aromatic amines, including 2-naphthylamine, 4-aminobiphenyl and benzidine, are known urinary bladder carcinogens in man and other species, but in rodents, aromatic amines and amides have usually induced liver tumors, occasionally also with tumors of the bladder and other tissues. Variations in organ specificity are related to differences in metabolism; for the production of bladder tumors, the rates of acetylation and deacetylation appear to be critical. Bladder specific carcinogens in rodents and other species have subsequently been identified, including N-butyl-N44-hydroxybutyl)nitrosamine (BBN) administered in the drinking water, N-[(445-nitro-2-furyl)-2-thiazolyllformamide (FANFT) in the diet and N-methyl-N-nitrosourea (MNU) instilled intravesically.When low doses of several bladder carcinogens (BBN, FANFT, 2-acetylaminofluorene, and 3,3'-dichlorobenzidine) are administered to rats, either simultaneously or sequentially, a synergistic effect is observed with respect to bladder carcinogenesis. In addition, a multistage carcinogenesis process has been demonstrated for the rat bladder using MNU or FANFT as initiators, and dietary sodium saccharin, sodium cyclamate, or tryptophan as promoters. Calculi (or pellets) appear to enhance the promotion process but are not necessary for it to occur. Recent studies also indicate that urine has a role in the promoting process. The urothelium normally has a very low mitotic rate. If mucosal proliferation is increased, such as during fetal development or during regeneration and repair of an ulcer, the bladder appears to be considerably more sensitive to the effects of promoting substances. For example, if sodium saccharin is administered to rats after ulceration of the bladder, even without prior administration of an initiator, bladder carcinoma develops. Under these conditions, the substance appears as a carcinogen. Human populations with increased bladder epithelial proliferation, such as fetus, infants, patients with bacterial cystitis or men with partially obstructive prostatism, may have increased susceptibility to the action of carcinogenic or promoting stimuli.

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Recombinogenicity and mutagenicity of saccharin in Saccharomyces cerevisiae

Cited by 23 publications

References 14 publications

Fungal Cell Wall Septation and Cytokinesis Are Inhibited by Bleomycins

Fungal Cell Wall Septation and Cytokinesis Are Inhibited by Bleomycins

Pelvic Osteotomies in Children and Adults - Experience of University Medical Centre Ljubljana

Promotion in Urinary Bladder Carcinogenesis

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