Carnosol, radiation and melanoma: a translational possibility.
OBJECTIVE
To compare the genoprotective and radioprotective effect of carnosol (COL) against damage induced by ionizing radiation with similar effects produced by different antioxidant compounds.


METHODS
The genoprotective effect was studied by means of the micronucleus test for antimutagenic activity in which the reduction in the frequency of micronuclei was evaluated in cytokinesis-blocked cells of human lymphocytes. The radioprotective effects were studied by cell viability test (MTT) in PNT2 (normal prostate) and B16F10 (melanoma) cell lines when they were administered before exposure to different X-ray doses (4, 6, 8, 10 and 0 Gy).


RESULTS
Carnosol shows a significant genoprotective capacity (p < 0.001) against radiation with a protection factor of 50 %, and a dose-reduction factor of 4.3. Cell survival obtained with COL administered before exposure to 10 Gy of X-rays showed a protection factor of 55.1 %, eliminating 39 % of radiation-induced cell death in normal epithelial cells of prostate (PNT2) (p < 0.001). However, in the melanoma cell lines (B16F10) assayed, COL acted not as a radioprotector, but as a sensitizing agent increasing the cellular death by 34 % (p < 0.01) and producing an enhancement ratio of 2.12.


CONCLUSIONS
Carnosol may be developed as a radioprotective agent in the non-tumoral cells. However, in the B10F16 melanoma cells, melanogenesis is activated by COL leading to redistribution of the enzymatic balances of glutathione and cysteine-lyase production, which could compromise the intracellular redox defence system. This effect appears as an increase in the capacity of ionizing radiation-induced damage, and thus exhibits a paradoxical protective effect of COL on melanoma cells.
Radiology and Physical Medicine Department, Faculty of Medicine/Dentistry, University of Murcia, 30100 Espinardo, Murcia, Spain. mab@um.es
M
M
Alcaraz
D G
DG
Achel
A
A
Olivares
E
E
Olmos
M
M
Alcaraz-Saura
J
J
Castillo
D045784:Abietanes / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival; D004307:Dose-Response Relationship, Radiation; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects; D008545:Melanoma / Q000532:radiotherapy* / Q000628:therapy*; D008546:Melanoma, Experimental; D051379:Mice; D015162:Micronucleus Tests; D010084:Oxidation-Reduction; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D012878:Skin Neoplasms / Q000532:radiotherapy* / Q000628:therapy*; D057170:Translational Research, Biomedical / Q000379:methods
D045784:Abietanes; D000975:Antioxidants; D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents; C068623:carnosol; D005978:Glutathione