1. Genotoxicity and Cytotoxicity Evaluation of
UNIVERSIDADE FEDERAL DE GOIÁS
INSTITUTE OF BIOLOGICAL SCIENCES
Genotoxicity and Cytotoxicity Evaluation of
the Neolignan Analogue 2-(4-Nitrophenoxy)-
1Phenylethanone and its Protective Effect
Against DNA Damage
ALEX LUCAS HANUSCH
-MASTER-

2. 2-(4-Nitrophenoxy)-1Phenylethanone
NEOLIGNANS
Anti-leishmanial,
Antifungal
Anxiolytic
Anti-inflammatory
Antitumor
Antioxidant activity
Reducing ischemic injury
Phenylpropanoid
Phenylpropanoid
2-(4-Nitrophenoxy)-1Phenylethanone
Lignan
Neolignan
Alex Lucas Hanusch
-Master-
UFG

3. GENOTOXICITY and ANTIGENOTOXICITY
  Many drugs can cause changes in the genetic material, accelerating carcinogenesis and the cell aging process (Kahl et al., 2012).
Genotoxic evaluations are conducted during pre-clinical trials (Brambilla & Martelli., 2009).
Important factors for lengthening human life span are cancer prevention and tumor control.
The development of chemopreventive agents is of great importance to be used in cancer therapies (Rhee & Park, 2001; Lourenço et al., 2010).
Alex Lucas Hanusch
-Master-
UFG

4. GENOTOXICITY and ANTIGENOTOXICITY
The mouse bone marrow micronucleus test is used in genotoxicity and cytotoxicity studies of chemicals.
Comet assay or single cell gel electrophoresis is used to genotoxicity evaluation. It is suitable to detect clastogenic compounds, but not aneugenic compounds.

5. AIM
The aim of this study was to evaluate the genotoxic and cytotoxic activities of the neolignan analogue 2-(4-nitrophenoxy)-1-phenylethanone (4NF) in mice and its protective effect against DNA damage.

6. Materials and Methods
The neolignan analogue 4NF was characterized by nuclear magnetic resonance of 1H and infrared technique, which showed a high degree of purity.
Alex Lucas Hanusch
-Master-
UFG

7. MOUSE BONE MARROW MICRONUCLEUS TEST Intraperitoneal administration
24 hours and 48 hours.
Cyclophosphamide at 50 mg.kg-1
Euthanasia
Genotoxicity PCE
Cytotoxicity ratio of PCE and NCE
Alex Lucas Hanusch
-Master-
UFG

8. COMET ASSAY Electrophoresis (pH > 13)
Lysis
Electrophoresis (pH > 13)
CASP (Comet Assay Software Project) version
It was assessed the DNA damage of 100 nucleoids
% DNA in the tail, the tail moment and Olive tail moment
Alex Lucas Hanusch
-Master-
UFG

9. RESULTS
Micronucleus test
Alex Lucas Hanusch
-Master-
UFG 9

10. RESULTS
Micronucleus test
Alex Lucas Hanusch
-Master-
UFG

11. RESULTS
Comet assay
Alex Lucas Hanusch
- Master-
UFG

12. RESULTS
Comet assay
Alex Lucas Hanusch
-Master-
UFG

13. DISCUSSION No genotoxic effect: micronucleus test and comet assay
Studies with neolignans also showed no genotoxic effect induced by these molecules.
LI et al (2007) found no genotoxic effects of a plant extract containing 94% of magnolol neolignan and 1.5% of honokiol neolignan.
Daurinol and cubebin lignans: Do not present genotoxic effects (Kang et al, 2011; Rezende et al, 2013.).
Alex Lucas Hanusch
-Master-
UFG

14. DISCUSSION
Cytotoxic: reduction ratio of PCE / NCE at a dose of 100mg.kg-1
The cytotoxicity is of great interest in the prevention and treatment of disease and is a promising characteristics for a candidate chemotherapeutic agent.
Studies have found lignoids with cytotoxic activity specific for some tumor cell lines, such as neolignan licarin A and the lignans galbacin, sesamin, machilin A and G (Lee et al, 2004;. SAEED et al, 2014).
Alex Lucas Hanusch
-Master-
UFG

15. DISCUSSION
Antigenotoxic and anticytotoxic: Micronucleus and Comet test.
OLIVEIRA JÚNIOR et al (2007) They observed a reduction in the number of micronuclei induced by cyclophosphamide in mice treated with grandidisin neolignan.
Magnolol neolignans Hinokinin and cubebin lignans They proved to be antimutagenic, antigenotoxic and antioxidants (SAITO et al., 2006; SAITO et al., 2008; MEDOLA et al., 2007; RESENDE et al., 2010; REZENDE et al., 2013; SINIGAGLIA et al., 2006).
Alex Lucas Hanusch
-Master-
UFG

16. CONCLUSION The 4NF did not exhibit genotoxicity.
Reduce cytotoxic and genotoxic effects of cyclophosphamide.
The possible use of this compound as a chemopreventive and/or therapeutic agent still requires further investigation using different mutagenicity/genotoxicity tests, long-term tests in animals, and research in molecular biology to carry out comprehensive studies of gene expression.
Alex Lucas Hanusch
-Master-
UFG

17. Thank you for your attention!
Alex Lucas Hanusch
-Master-
UFG