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1

Heterocyclic aromatic amines and their role in the induction of carcinogenesis

100%
Woziwodzka A., Piosik J.
Biotechnologia
|
2009
|
issue 4
133-151
EN
Cancer is one of the most frequent causes of human death worldwide. It is a consequence of inherited DNA impairments or mutations induced by several exogenous factors. Diet is one of the most important exogenous factors, which is responsible for one-third cancer incidents in humans. Heterocyclic aromatic amines (HCA) arise during thermal processing of food. Based on the results on rodents and epidemiological data IARC classified HCA as probably (class 2A) or possibly (class 2B) carcinogenic to humans. After metabolic activation by cytochrome P450, N-hydroxy derivatives of HCA demonstrate strong mutagenic activity as they can form adducts with DNA. Experiments on laboratory animals indicated that HCA induce digestive tract, breast and lung cancers. Epidemiological data also confirm the association between HCA consumption and cancer appearance in humans. Although it is impossible to completely eliminate HCA from diet, there are several ways to limit the exposure to HCA and decrease their negative impact on human organisms.
2

Mutagenic activity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

100%
Ulanowska K., Wegrzyn G.
Journal of Applied Genetics
|
2006
|
vol. 47
|
issue 1
85-87
EN
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxin, which can damage dopaminergic neurons. It causes symptoms resembling those observed in patients suffering from Parkinson's disease, and hence this toxin is widely used in studies on animal models of this disorder. Mutagenicity of MPTP was also reported by some authors, but results obtained by others suggested that this compound is not mutagenic. Interestingly, those contrasting results were based on the same assay (the Ames test). Therefore, we aimed to test MPTP mutagenicity by employing a recently developed Vibrio harveyi assay, which was demonstrated previously to be more sensitive than the Ames test, at least for some mutagens. We found that MPTP showed a significant mutagenic activity. Moreover, MPTP mutagenicity was attenuated by methylxanthines, compounds that are known to form complexes with aromatic mutagens.
3

Induction of light emission by luminescent bacteria treated with UV light and chemical mutagens

75%
Czyz A., Plata K., Wegrzyn G.
Journal of Applied Genetics
|
2002
|
vol. 43
|
issue 3
377-389
EN
Intensity of light emission by luminescent bacteria in response to UV irradiation and chemical mutagens was tested. We demonstrated that luminescence of six strains of marine bacteria (belonging to four species: Photobacterium leiognathi, P. phosphoreum, Vibrio fischeri and V. harveyi) is significantly increased by UV irradiation relatively shortly after dilution of cultures. Such a stimulation of luminescence was abolished in cells treated with chloramphenicol 15 min before UV irradiation, indicating that effective gene expression is necessary for UV-mediated induction of light emission. These results suggest that stimulation of luminescence in UV-irradiated bacterial cells may operate independently of the quorum sensing regulation. A significant induction of luminescence was also observed upon treatment of diluted cultures of all investigated strains with chemical mutagens: sodium azide (SA), 2-methoxy-6-chloro-9-(3-(2-chloroethyl)aminopropylamino)acridine ? 2HCl (ICR-191), 4-nitro-o-phenylenediamine (NPD), 4-nitroquinolone-N-oxide (NQNO), 2-aminofluorene (2-AF), and benzo[?]pyrene. These results support the proposal that genes involved in bioluminescence belong to the SOS regulon. The use of bacterial luminescence systems in assays for detection of mutagenic compounds is discussed in the light of this proposal.
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