Effect of epithalon on the incidence of chromosome aberrations in senescence-accelerated mice.

The incidence of chromosome aberrations in bone marrow cells of 12-month-old SAMP-1 female mice characterized by accelerated aging was 1.8 times higher than in wild-type SAMR-1 females and 2.2 times higher than in SHR females of the same age. Treatment with Epithalon (Ala-Glu-Asp-Gly) starting from the age of 2 months decreased the incidence of chromosome aberrations in SAMP-1, SAMR-1, and SHR mice by 20%, 30.1%, and 17.9%, respectively, compared to age-matched controls (p<0.05). Treatment with melatonin (given with drinking water in a dose of 20 mg/liter in night hours) had no effect on the incidence of chromosome aberrations in SHR mice. These data indicate antimutagenic effect of Epithalon, which probably underlies the geroprotective effect of this peptide.

[The influence of melatonin on mutagenicity and antitumor action of cytostatic drugs in mice]. / Vliianie melatonina na mutagennost' i protivoopukholevyi éffekt tsitostatikov u myshei.

SHR mice received single injections of N-nitrosomethylurea (NMU, 50 mg/kg, i.p.), cyclophosphamide (CP, 200 mg/kg, i.p.) or 1,2-dimethylhydrazine (DMH, 15 mg/kg, s.c.) alone or in combination with melatonin (5 mg/kg, s.c.). For mutagenic study chromosome aberrations tests (ChA) in bone marrow cells and sperm head anomaly test (SHA) were used. Melatonin did not appear mutagenic in either of the tests and significantly reduced the level of ChA (%) from 16.9 +/- 1.6 (NMU), 13.7 +/- 3.5 (CP) and 8.7 +/- 0.3 (DMH) to 4.5 +/- 0.6, 4.3 +/- 0.9 and 5.6 +/- 0.2, respectively, (p < 0.05). Similarly, SHA frequency (%) under the melatonin influence was reduced from 18.6 +/- 0.4 (NMU), 17.7 +/- 0.4 (CP) and 10.0 +/- 0.5 (DVH) to 9.9 +/- 0.5, 6.1 +/- 0.3 and 7.5 +/- 0.2, respectively, (p < 0.05). Unlike in controls, exposure to melatonin in drinking water (20 mg/l, at night) or in injections (5 mg/kg, s.c.) alone or in combination with NMU or CP failed to influence subcutaneously-transplanted Ehrlich carcinoma growth. These findings suggest that melatonin reduced the mutagenicity of the cytostatic drugs without affecting their anti-tumor action.