RESUMO

Cisplatin, carboplatin, and oxaliplatin are some of the most often used alkylating chemotherapeutic agents. In view of the paucity of data on the genotoxicity of oxaliplatin, this study compares the mutagenic activity of cisplatin (0.006, 0.012, 0.025, 0.05 mM), carboplatin (0.1, 0.2, 0,5, 1.0 mM), and oxaliplatin (0.1, 0.2, 0,5, 1.0 mM) using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. Standard and high-bioactivation crosses of the drosophilid were used, which present basal and high levels of cytochrome P450 (CYP450) metabolization enzymes, respectively. All concentrations of cisplatin and carboplatin induced lesions in genetic material in both crosses, while oxaliplatin was mutagenic only to high bioactivation flies treated with 0.1, 0.5 and 1 mM of the compound. No significant differences were observed between genotoxicity values of cisplatin and carboplatin. However, CYP450 enzymes may have affected the mutagenic action of oxaliplatin. Carboplatin induced mainly mutation events, while cisplatin triggered mostly mutation and recombination events when low and high doses were used. Most events induced by oxaliplatin were generated by somatic recombination. Important differences were observed in genotoxic potential of platinum chemotherapeutic compounds, possibly due to the origin and type of the lesions induced in DNA and the repair mechanisms involved.

Assuntos

RESUMO

Abacavir (ABC), zidovudine (AZT), and lamivudine (3TC) are nucleoside analog reverse transcriptase inhibitors (NRTIs) widely used as combination-based antiretroviral therapy against human immunodeficiency virus. Despite effective viral suppression using NRTI combinations, genotoxic potential of NRTIs can be increased when administered in combination. This study investigated the toxic and genotoxic potential of ABC when administered alone or in combination with AZT and/or 3TC using the somatic mutation and recombination test in Drosophila melanogaster. This test simultaneously evaluated two events related to carcinogenic potential: mutation and somatic recombination. The results indicated that ABC was responsible for toxicity when administered alone or in combination with AZT and/or 3TC. In addition, all treatment combinations increased frequencies of mutation and somatic recombination. The combination of AZT/3TC showed the lowest genotoxic activity compared to all combinations with ABC. Therefore, our results indicated that ABC was responsible for a significant portion of genotoxic activity of these combinations. Somatic recombination was the main genetic event observed, ranging from 83.7% to 97.7%.

Assuntos

RESUMO

The significant contents of artepillin C (AC) in green propolis have prompted research on the biological activities of the compound. The present study evaluated the activity of this phenolic compound on DNA, assessing its genotoxic and antigenotoxic potentials in the somatic mutation and recombination test in Drosophila melanogaster. The standard (ST) and high-bioactivation (HB) crosses were used in the assessment of genotoxic potential, since they express cytochrome P450 metabolization enzymes differently. In the 0.1-1.6 mM concentration range, AC did not have any genotoxic action in either cross. Antigenotoxic potential was investigated using the ST cross. In co- and post-treatment protocols, AC 0.4, 0.8, and 1.6 mM did not modulate mutagenic action of ethyl methanesulphonate. However, though it did not influence the frequency of damage induced by mitomycin C in co-treatment, AC reduced genotoxicity of the mutagen when administered after damage, but only at 0.4 mM. This modulation is associated with the reduction of genetic damage caused by recombinational events. The results of the present study and literature findings indicate that the various responses elicited by AC, namely induction of DNA damage, production of genetic lesions, or activation of DNA repair mechanisms are functions of AC concentration.

Assuntos

RESUMO

Propolis is a resinous, complex mixture of compounds collected by the bee species Apis mellifera. This study investigated the genotoxicity of green and brown propolis collected in southeast Brazil using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. The effect of five concentrations (0.5, 1.0, 2.0, 4.0, and 7.5 mg/mL) of both propolis types was analyzed in standard (ST) and high-bioactivation (HB) crosses, which have normal and high levels of cytochrome P450 enzymes, respectively. The results show that the types of propolis evaluated have no mutagenic action, in either cross. Moreover, chromatography findings revealed that the propolis types analyzed have different chemical compositions. Brown propolis had lower levels of polyphenols (∼7.2 mg/mL), compared to the green type (34.9 mg/g). Taken together, the findings of the present study and literature reports point to the safety in consuming low amounts of propolis, considering the risk of genetic damage, and confirm the absence of mutagenic and recombinagenic actions of the propolis types investigated.

Assuntos

RESUMO

With the aim of a better characterization of the somatic recombination process in Trichoderma pseudokoningii, a progeny from crossings between T. pseudokoningii strains contrasting for auxotroph markers was characterized by RAPD markers and PFGE (electrophoretic karyotype). Cytological studies of the conidia, conidiogenesis and heterokaryotic colonies were also performed. The genotypes of the majority of the recombinant strains analyzed were similar to only one of the parental strains and the low frequency of polymorphic RAPD bands suggested that the nuclear fusions may not occur into the heterokaryon. In some heterokaryotic regions the existence of intensely staining hyphae might be related to cell death. We proposed that a mechanism of somatic recombination other than parasexuality might occur, being related to limited vegetative compatibility after postfusion events, as described for other Trichoderma species.

Assuntos

RESUMO

With the aim of a better characterization of the somatic recombination process in Trichoderma pseudokoningii, a progeny from crossings between T. pseudokoningii strains contrasting for auxotroph markers was characterized by RAPD markers and PFGE (electrophoretic karyotype). Cytological studies of the conidia, conidiogenesis and heterokaryotic colonies were also performed. The genotypes of the majority of the recombinant strains analyzed were similar to only one of the parental strains and the low frequency of polymorphic RAPD bands suggested that the nuclear fusions may not occur into the heterokaryon. In some heterokaryotic regions the existence of intensely staining hyphae might be related to cell death. We proposed that a mechanism of somatic recombination other than parasexuality might occur, being related to limited vegetative compatibility after postfusion events, as described for other Trichoderma species.

RESUMO

With the aim of a better characterization of the somatic recombination process in Trichoderma pseudokoningii, a progeny from crossings between T. pseudokoningii strains contrasting for auxotroph markers was characterized by RAPD markers and PFGE (electrophoretic karyotype). Cytological studies of the conidia, conidiogenesis and heterokaryotic colonies were also performed. The genotypes of the majority of the recombinant strains analyzed were similar to only one of the parental strains and the low frequency of polymorphic RAPD bands suggested that the nuclear fusions may not occur into the heterokaryon. In some heterokaryotic regions the existence of intensely staining hyphae might be related to cell death. We proposed that a mechanism of somatic recombination other than parasexuality might occur, being related to limited vegetative compatibility after postfusion events, as described for other Trichoderma species.

RESUMO

Crossing experiments via hyphal anastomosis between two strains contrasting for auxotrophic markers of Trichoderma pseudokoningii were conducted to characterize the somatic recombination process in this specie. Four crossings were made and a total of 1052 colonies obtained from conidial suspensions of the heterokaryotic colonies were analyzed. Sixty-eight recombinant colonies, from four growing generations, were analyzed for the auxotrophic markers. Of the 68 colonies analyzed, 58 were stable after four generations and the remainders were unstable, reverting to one of the parentals. Most of the recombinant colonies were unstable through subculture and after four growing generations they showed the leu ino met markers (auxotrophic for leucin, inositol and metionin respectively). The unstable recombinant colonies showed irregular growing borders, sparse sporulation and frequent sector formation. The results suggest the occurrence of recombination mechanisms in the heterokaryon (somatic recombination), different from those described for the parasexual cycle or parameiosis. Therefore, we proposed the ocurrence of nuclei degradation from one parental (non prevalent parental) in the heterokaryon and that the resulting chromosomal fragments may be incorporated into whole nuclei of the another parental (prevalent parental). However the parameiosis as originally described cannot be excluded.

Com o objetivo de se caracterizar o processo de recombinação somática em Trichoderma pseudokoningii, foram realizados cruzamentos via anastomose de hifas entre duas linhagens desta espécie, contrastantes para os marcadores de auxotrofia. Foram realizados quatro cruzamentos, sendo analisadas um total de 1052 colônias obtidas a partir de suspensões de conídios provenientes das colônias heterocarióticas. Foram analisadas sessenta e oito colônias recombinantes em quatro gerações de crescimento, sendo verificados os marcadores de auxotrofia. Das 68 colônias, 58 se mostraram estáveis após quatro gerações de crescimento e as colônias restantes permaneceram instáveis, revertendo para as marcas de uma das linhagens parentais. A maioria das colônias se mostrou instável através das gerações de subcultivo, e após quatro gerações de crescimento estas apresentaram as marcas de auxotrofia leu ino met (auxotrofia para leucina, inositol e metionina, respectivamente). As colônias recombinantes instáveis apresentaram bordas irregulares de crescimento, esporulação esparsa e a freqüente formação de setores. Os resultados sugerem a ocorrência de mecanismos de recombinação no heterocário (recombinação somática), diferente daqueles descritos para o ciclo parassexual ou parameiose, sendo proposto a ocorrência da degradação no heterocário de núcleos provenientes de uma das linhagens parentais (parental não prevalente) e a incorporação de fragmentos cromossômicos nos núcleos íntegros da outra linhagem parental (parental prevalente). No entanto a parameiose, como originalmente descrita, não pode ser excluída.