Evaluation of Genotoxic Effects of New Molecules with Possible Trypanocidal Activity for Chagas Disease Treatment
Table 6
PTAL 04-09 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
1.0
85 ± 95 (0.98)
97
74 ± 13 (0.76)
77
5.0
100 ± 5.7 (1.15)
100
80 ± 13 (0.82)
73
10
115 ± 16 (1.33)
100
78 ± 16 (0.80)
77
50
143 ± 11 (1.65)
100
82 ± 9.6 (0.85)
77
TA98
0
45 ± 1.5 (1.00)
100
18 ± 6.4 (1.00)
100
1.0
66 ± 11 (1.46)
93
18 ± 8.5 (0.98)
100
5.0
64 ± 3.0 (1.40)
100
17 ± 2.8 (0.91)
100
10
65 ± 5.1 (1.43)
100
15 ± 1.5 (0.82)
71
50
66 ± 7.0 (1.45)
100
16 ± 2.0 (0.88)
62
TA100
0
120 ± 23 (1.00)
100
117 ± 19 (1.00)
100
1.0
113 ± 12 (0.94)
100
129 ± 18 (1.11)
66
5.0
165 ± 12 (1.37)
100
144 ± 14 (1.23)
59
10
192 ± 9.4 (1.59)
100
169 ± 9.4 (1.45)
60
50
439 ± 39 (3.64*)
100
297 ± 12 (2.53*)
55
TA1535
0
22 ± 3.2 (1.00)
100
5.3 ± 1.5 (1.00)
100
1.0
21 ± 1.5 (0.94)
97
7.3 ± 1.1 (1.38)
41
5.0
24 ± 2.0 (1.09)
95
8.3 ± 2.3 (1.56)
41
10
25 ± 4.5 (1.10)
100
8.6 ± 1.1 (1.63)
39
50
26 ± 1.5 (1.18)
93
5.6 ± 1.1 (1.06)
36
TA102
0
254 ± 16 (1.00)
100
265 ± 12 (1.00)
100
1.0
258 ± 19 (1.02)
100
266 ± 24 (1.01)
100
5.0
262 ± 24 (1.03)
100
248 ± 9.1 (0.94)
100
10
262 ± 31 (1.03)
100
260 ± 30 (0.98)
100
50
274 ± 16 (1.08)
100
265 ± 7.6 (1.00)
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.
