Evaluation of Genotoxic Effects of New Molecules with Possible Trypanocidal Activity for Chagas Disease Treatment
Table 5
PAMT 09 induction of mutagenicity and cytotoxicity in Salmonella enterica serovar Typhimurium standard strains, without (−S9) and with (+S9) metabolic activation.
Strains
Dose (g/mL)
−S9
+S9
Mean ± S.D. (M.I.a)
Survivalb
Mean ± S.D. (M.I.a)
Survivalb
TA97
0
87 ± 9.8 (1.00)
100
97 ± 25 (1.00)
100
0.05
89 ± 4.5 (1.02)
100
74 ± 5.5 (0.76)
100
0.1
87 ± 3.6 (1.02)
95
84 ± 7.3 (0.87)
96
0.5
92 ± 4.9 (1.07)
85
87 ± 2.0 (0.90)
95
1.0
81 ± 1.4 (0.93)
83
80 ± 8.7 (0.82)
100
TA98
0
45 ± 1.5 (1.00)
100
18 ± 6.4 (1.00)
100
0.05
58 ± 9.6 (1.28)
100
17 ± 1.0 (0.91)
100
0.1
66 ± 3.0 (1.46)
93
17 ± 0.5 (0.93)
100
0.5
50 ± 5.8 (1.10)
97
21 ± 4.0 (1.14)
100
1.0
48 ± 5.8 (1.07)
78
32 ± 9.0 (1.73)
74
TA100
0
120 ± 23 (1.00)
100
117 ± 19 (1.00)
100
0.05
100 ± 18 (0.83)
100
104 ± 11 (0.89)
73
0.1
96 ± 9.5 (0.80)
100
126 ± 12 (1.08)
73
0.5
95 ± 9.1 (0.79)
100
107 ± 2.6 (0.91)
72
1.0
100 ± 14 (0.83)
100
107 ± 10 (0.92)
71
TA1535
0
22 ± 3.2 (1.00)
100
5.3 ± 1.5 (1.00)
100
0.05
19 ± 1.1 (0.94)
100
7.5 ± 0.7 (1.41)
68
0.1
19 ± 2.3 (0.92)
100
9.5 ± 2.1 (1.78)
55
0.5
32 ± 5.5 (1.56)
100
8.6 ± 1.5 (1.63)
59
1.0
25 ± 0.5 (1.21)
85
7.0 ± 1.0 (1.31)
58
TA102
0
254 ± 16 (1.00)
100
265 ± 12 (1.00)
100
0.05
285 ± 30 (1.12)
79
275 ± 17 (1.04)
100
0.1
289 ± 9.0 (1.14)
76
242 ± 11 (0.91)
100
0.5
282 ± 28 (1.11)
73
256 ± 10 (0.97)
100
1.0
307 ± 24 (1.21)
60
240 ± 27 (0.91)
100
Mutagenic index (M.I.): ratio of the his + induced with samples/spontaneous his + in the negative control. S.D.: standard deviation. Positive responses marked in bold when M.I. ≥ 2.
bPercent of cellular survival: <70% was considered toxic dose and it is marked in bold.
*Representation of a significant response (). Negative control was DMSO. Positive controls and their M.I., with and without S9 mix, respectively, were: 4NQO (7.19) and 2AA (9.55) for TA97, 4NQO (10) and 2AA (3.95) for TA98; AS (13) and 2AA (2.10) for TA100, AS (18) and 2AA (6.25) for TA1535, and MitC (9.28 and 6.86) for TA102.
