The in vivo genotoxicity of cisplatin, isoflurane and halothane evaluated by alkaline comet assay in Swiss albino mice

Abstract

The aim of this study was to evaluate the genotoxicity of repeated exposure to isoflurane or halothane and compare it with the genotoxicity of repeated exposure to cisplatin. We also determined the genotoxicity of combined treatment with inhalation anaesthetics and cisplatin on peripheral blood leucocytes (PBL), brain, liver and kidney cells of mice. The mice were divided into six groups as follows: control, cisplatin, isoflurane, cisplatin-isoflurane, halothane and cisplatin-halothane, and were exposed respectively for three consecutive days. The mice were treated with cisplatin or exposed to inhalation anaesthetic; the combined groups were exposed to inhalation anaesthetic after treatment with cisplatin. The alkaline comet assay was performed. All drugs had a strong genotoxicity (P<0.05 vs. control group) in all of the observed cells. Isoflurane caused stronger DNA damage on the PBL and kidney cells, in contrast to halothane, which had stronger genotoxicity on brain and liver cells. The combination of cisplatin and isoflurane induced lower genotoxicity on PBL than isoflurane alone (P<0.05). Halothane had the strongest effect on brain cells, but in the combined treatment with cisplatin, the effect decreased to the level of cisplatin alone. Halothane also induced the strongest DNA damage of the liver cells, while the combination with cisplatin increased its genotoxicity even more. The genotoxicity of cisplatin and isoflurane on kidney cells were nearly at the same level, but halothane caused a significantly lower effect. The combinations of inhalation anaesthetics with cisplatin had stronger effects on kidney cells than inhalation anaesthetics alone. The observed drugs and their combinations induced strong genotoxicity on all of the mentioned cells.

Ascorbic Acid (Vitamin C)-Mediated Protection on Mutagenic Potentials of Cisplatin in Mice Bearing Ascites Dalton ’s Lymphoma

“…Bone marrow cells are susceptible to oxidative damage and sensitive to clastogenic chemicals so, it has been commonly used for screening of mutagenicity and/or antimutagenicity property of chemicals (Umegaki et al, 1997). The results of present investigation showed development of these mutagenic parameters after cisplatin alone or combination treatment of tumor-bearing mice and supports the earlier findings of its genotoxic properties (Adler and El-Tarras, 1989;Brozovic et al, 2011). The chromosomal aberration pattern revealed that chromatid breaks and fragments occurred more frequently after cisplatin treatment (Fig.…”

Anesthetic Isoflurane Induces DNA Damage Through Oxidative Stress and p53 Pathway

“…Brozovic et al reported that isoflurane induced DNA damage in peripheral blood leucocytes and kidney cells of Swiss albino mice by using alkaline comet assay [64]. However, other studies did not investigate the underlying mechanisms.…”

Comet Assay on Toxicogenetics; Several Studies in Recent Years on Several Genotoxicological Agents

“…Comet Assay cannot directly distinguish between the dead cells and the cells that have a heavily damaged DNA [23].…”

“…In both B and T cells DNA damage levels were found significant and dose-dependent, importantly DNA damage level in B lymphocytes was higher than in T lymphocytes [59]. Many chemicals compounds were used by Toyoizumi et al, to assess the specificity and the sensibility of skin comet assay, chemicals treated used were N-methyl-N -nitro-N-nitrosoguanidine (MNNG, 0.0125-0.2%), 4-nitroquinoline-1-oxide (4NQO,0.01-0.25%), mitomycinC(MMC,0.0125-0.05%), benzo [a] pyrene (B[a]P, 0.25-2%), and 7,12-dimethylbenz[a]anthracene (DMBA, 0.25-1%) and they applied it to the dorsal skin of hairless male mice [23]. In their study they confirmed that in vivo skin comet assay utile technique able to detect DNA damage induced on the skin by chemicals genotoxic [60].…”

“…Alteration of kidney cells DNA and peripheral blood leucocytes (PBL) harder DNA damage were found in Isoflurane exposure, indeed halothane caused genotoxicity on liver cells and brain. For the gentoxicity of cisplatin, it caused a lower genotoxicity in combination with isoflurane on peripheral blood leucocytes in comparaison with isoflurane alone [23]. Monteiro Neto et al, studied the genotoxic potential of artepillin C and its ability to reduce the chemically caused chromosome breakage or loss and the primary DNA damage using in male Swiss mice.…”