Mutagenic Action of Nitrofurans on Euglena gracilis and Mycobacterium phlei

Abstract

There is a pronounced difference between the action of antibiotics and nitrofurans on Euglena gracilis . Those antibiotics that induce hereditary loss of chloroplasts do so only when they affect dividing cells. On the other hand, nitrofurans induce a mass mutation in both dividing and nondividing cells (under conditions of continuous illumination of cultures). It was found that a breakdown product, 5-nitro-2-furaldehyde, is liberated from furadantin and furoxone. This intermediate is responsible for the observed specific mutagenicity of 5-nitrofuran drugs. The mutagenic action of 5-nitro-2-furaldehyde is very similar to that of nitrosoguanidine. Both compounds induce bleached mutants of E. gracilis when acting on growing or resting cells, regardless of the dark or light conditions. Similarly, both compounds induce reverse mutations in auxotrophic strains of Mycobacterium phlei .

Hyperthermia and other factors increasing sensitivity of Euglena to mutagens and carcinogens

“…This hereditary bleaching of Euglena gracils was shown to be caused by physical factors such as elevated temperature [30], UV radiation [22], and chemical compounds such as antibiotics [4-7, lo], nitrofurans [8,9,[11][12][13][14][15][16][17][18]23,24], nitrosoguanidine and related compounds [ 11,25,26], and other factors as well. The hereditary bleaching results in a conversion of original green colonies to apochlorotic white ones, and hence, the detection of this phenomenon is very simple.…”

Quinolones and coumarins eliminate chloroplasts from Euglena gracilis

“…That these agents are able to eliminate chloroplasts from both growing and nongrowing cells suggests the presence of more than one mechanism of chloroplast antagonism, as has been suggested for killing of bacteria by ciprofloxacin and ofloxacin (16,26,28,31) and even norfloxacin (27) based on similar types of studies. These findings are also remarkable in that previously evaluated antibiotics eliminated E. gracilis chloroplasts only from growing cells (6)(7)(8)(9). In contrast, mutagens and carcinogens eliminated chloroplasts from either growing or nongrowing cells (3,8,9).…”

“…These findings are also remarkable in that previously evaluated antibiotics eliminated E. gracilis chloroplasts only from growing cells (6)(7)(8)(9). In contrast, mutagens and carcinogens eliminated chloroplasts from either growing or nongrowing cells (3,8,9). We recently identified differences between DNA gyrase inhibitors and classical mutagens in their action on E. gracilis chloroplasts.…”

“…These organelles are semiautonomous (with their own DNA and protein synthesis apparatus) and appear to be of eubacterial origin (9,10,13,21). We previously demonstrated that chloroplasts of the flagellate Euglena gracilis are susceptible to antibacterial agents and other biologically active compounds (3,(6)(7)(8)(9)(10). In contrast to the higher plants, chloroplasts in E. gracilis are not essential, thus placing this unicellular eucaryotic microorganism on the boundary between the plant and animal kingdoms.…”

Genetic analysis of ad‐3 mutants induced by AF‐2 and two other nitrofurans in neurospora crassa

“…It is not known, however, which reduction product (NO, NHOH, or NH2) is responsible for their mutagenic and carcinogenic activities. It has also been suggested that 5-nitro-2-furaldehyde, the breakdown product of nitrofuran, is the active form of nitrofuram [9] . Comparison of the complementation patterns among the AF-2-induced ad-3B mutants and those induced by other chemical agents at comparable forward-mutation frequencies (50-100/1 O6 survivors) indicates that AF-2 and the monofunctional alkylating agents ethylenimine and ICR-177 cause similar spectra of intragenic alterations in N crassa (Table IV).…”