Clastogenic activity of integerrimine determined in mouse micronucleus assays

The pyrrolizidine alkaloid integerrimine, obtained from Senecio brasiliensis, was tested by acute dosing at two concentrations (18.75 and 37.5 mg/kg), and at different times, to establish its ability to induce micronuclei in mouse erythrocytes. This alkaloid was able to increase the frequency of micronucleated polychromatic erythrocytes in both, bone marrow and peripheral blood erythrocytes

Authorship

Maria Clara Gimmler-Luz

Universidade Federal do Rio Grande do Sul, Departamento de Genética, Instituto de Biociências, Rio Grande do Sul, BrazilUniversidade Federal do Rio Grande do SulBrazilRio Grande do Sul, BrazilUniversidade Federal do Rio Grande do Sul, Departamento de Genética, Instituto de Biociências, Rio Grande do Sul, Brazil

Bernardo Erdtmann

SCIMAGO INSTITUTIONS RANKINGS

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Tables (2)

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No. of animals Dose (mg/kg) Sample timeaTS A Sex No. of analyzed PCE mPCE/1000 PCE (individual data)Mean ± SD PCE/NCE ± SD N. Control 4 4 4 M 8,000 3.5, 3, 4.5, 3.5 3.6 ± 1.30 0.86 ± 0.42 5 5 5 F 10,000 5, 5.5, 4.5, 0, 1 3.0 ± 2.71 1.10 ± 0.52 PA 24 h 5 5 4 M 8,000 5, 8, 8.5, 4.5 6.5 ± 2.38* 0.50 ± 0.16 (18.75) 5 5 5 F 10,000 1, 4, 4, 1, 2 2.4 ± 1.52 0.48 ± 0.23 48 h 5 5 5 M 10,000 6, 5, 4, 2.5, 5 4.6 ± 1.67 0.65 ± 0.17 5 5 5 F 10,000 4, 8, 5, 6, 4 5.4 ± 1.67* 0.52 ± 0.18 72 h 5 4 4 M 8,000 8, 4, 4, 4 5.0 ± 2.00* 0.70 ± 0.18 5 5 5 F 10,000 2.5, 6, 4, 5, 3.5 4.2 ± 1.48 0.60 ± 0.43 PA 24 h 5 5 4 M 8,000 5.5, 2.3, 5.5, 3 4.0 ± 1.67 0.79 ± 0.14 (37.50) 5 5 5 F 10,000 8.5, 4.5, 3.5, 3.5, 7.6 5.5 ± 2.37* 0.78 ± 0.16 48 h 5 5 5 M 10,000 6, 6, 6.5, 8.5, 7 6.8 ± 1.30* 0.85 ± 0.44 5 5 5 F 10,000 0.5, 3.5, 4.5, 3, 5 3.3 ± 1.75 0.76 ± 0.38 72 h 5 4 4 M 8,000 2.5, 3, 2.5, 3.5 2.9 ± 0.48 0.54 ± 0.28 5 5 5 F 10,000 5, 3, 2, 3, 6 3.8 ± 1.64 0.55 ± 0.20 P. Control 24 h 9 9 9 M 18,000 23, 19, 31, 18, 28.19, 34.5, 23, 22.3 24.2 ± 5.76* 0.61 ± 0.22 7 7 7 F 14,000 33, 16, 18, 13.5, 20, 40, 27.3 24.0 ± 9.78* 0.59 ± 0.19 48 h 5 5 5 M 10,000 15.5, 17, 13, 9.5, 11.5 13.3 ± 3.01* 0.31 ± 0.06* 5 5 5 F 10,000 15, 12.5, 6.5, 11, 8 10.6 ± 3.42* 0.39 ± 0.30*

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Dose (mg/kg) Sample timeaNo. of animals Sex No. of analyzed PCE mPCE/1000 PCE (individual data) Means ± SD PCE/NCE ± SD T S A N. Control 9 9 8 M 24,000 3, 3, 1, 3.5, 2.5, 1, 1.5, 0 1.9 ± 1.24 55.20 ± 17.98 10 10 10 F 25,000 1, 1, 2, 2, 1, 0, 1, 0.5, 1, 1 1.0 ± 0.60 76.20 ± 26.18 PA 24 h 5 5 4 M 8,000 8.6, 4.6, 7.5, 7.5 7.1 ± 1.71* 66.00 ± 42.70 (18.75) 5 5 4 F 6,000 1, 1, 2, 2 1.5 ± 0.58 46.00 ± 12.98* 48 h 11 11 10 M 17,000 3, 2.5, 2.5, 2, 3, 1, 1, 1, 3, 1 2.0 ± 0.91 53.82 ± 22.71 10 10 10 F 14,000 1.5, 2.5, 1, 3, 1, 0, 4.2, 1, 1 1.7 ± 1.18 60.38 ± 24.24 72 h 5 4 4 M 5,000 2, 1, 4, 4 2.3 ± 1.99 61.50 ± 20.61 5 5 5 F 5,000 2, 2, 1, 1, 1 1.4 ± 0.55 52.60 ± 12.78 4 d 6 6 6 M 6,000 0, 3, 1, 0, 1, 5 1.7 ± 1.97 75.33 ± 18.99 5 5 5 F 5,000 4, 1, 1, 3, 4 2.6 ± 1.52* 73.20 ± 22.95 7 d 6 6 4 M 4,000 1, 0, 1, 0 0.5 ± 0.58 87.80 ± 61.11 5 5 4 F 4,000 0, 1, 0, 0 0.3 ± 0.50 56.40 ± 12.99 14 d 6 6 5 M 5,000 4, 4, 2, 1, 1 2.4 ± 1.52 55.20 ± 30.24 5 5 4 F 4,000 2, 1, 1, 2 1.5 ± 0.58 43.40 ± 28.17 21 d 6 6 5 M 5,000 0, 0, 1, 0, 0 0.2 ± 0.45 61.17 ± 15.00 5 5 5 F 5,000 2, 0, 0, 0, 1, 0 0.6 ± 0.89 53.25 ± 2.99 PA 24 h 5 4 4 M 8,000 3.5, 7.5, 1.5, 6.5 4.7 ± 2.92* 41.80 ± 8.66 (37.50) 5 5 5 F 5,000 6, 6, 2, 2, 7 4.6 ± 2.41* 57.80 ± 32.97 48 h 12 12 10 M 14,000 5.5, 4, 7, 7, 10, 6, 4, 10, 7, 11 7.2 ± 2.47* 46.60 ± 23.86 11 11 11 F 15,000 2.5, 5, 6, 6.5, 6.5, 7, 12, 4, 5, 5, 1 5.5 ± 2.81* 50.50 ± 13.16 72 h 5 4 4 M 7,000 4.5, 3.5, 4, 2 3.5 ± 1.27 38.00 ± 10.12 5 5 5 F 7,000 3, 1, 4, 1.5, 5 2.9 ± 1.67* 45.70 ± 5.86* 4 d 7 6 6 M 6,000 3, 2, 3, 2, 3, 3 2.7 ± 0.52 99.00 ± 25.18* 6 6 6 F 5,000 2, 1, 6, 0, 0, 1 1.7 ± 2.25 93.80 ± 12.00 7 d 7 6 5 M 5,000 1, 0, 2, 5, 6 2.8 ± 2.59 29.00 ± 1.73* 6 6 4 F 4,000 1, 1, 1, 2 1.3 ± 0.50 37.00 ± 9.86* 14 d 7 6 5 M 5,000 0, 1, 3, 1, 2 1.4 ± 1.14 63.40 ± 19.76 6 6 5 F 5,000 1, 4, 3, 2, 1 2.2 ± 1.30 49.20 ± 19.03 21 d 7 6 5 M 5,000 2, 0, 0, 0, 0 0.4 ± 0.89 63.50 ± 15.72 6 6 6 F 6,000 0, 0, 0, 0, 1, 0 0.2 ± 0.41 47.80 ± 7.86* P. Ccontrol 24 h 5 5 5 M 5,000 9, 10, 9, 5, 12 9.0 ± 2.55* 5 5 5 F 9,000 10, 9, 9, 9.5, 10 9.5 ± 0.50* 48 h 5 5 5 F 5,000 23, 35, 24, 26, 29 27.5 ± 4.83* 46.20 ± 12.40 5 5 5 F 5,000 13, 19, 22, 12, 21 17.4 ± 4.62* 37.40 ± 13.26*

		No. of animals
Dose (mg/kg)	Sample time^a	T	S	A	Sex	No. of analyzed PCE	mPCE/1000 PCE (individual data)	Mean ± SD	PCE/NCE ± SD
N. Control		4	4	4	M	8,000	3.5, 3, 4.5, 3.5	3.6 ± 1.30	0.86 ± 0.42
		5	5	5	F	10,000	5, 5.5, 4.5, 0, 1	3.0 ± 2.71	1.10 ± 0.52
PA	24 h	5	5	4	M	8,000	5, 8, 8.5, 4.5	6.5 ± 2.38*	0.50 ± 0.16
(18.75)		5	5	5	F	10,000	1, 4, 4, 1, 2	2.4 ± 1.52	0.48 ± 0.23
	48 h	5	5	5	M	10,000	6, 5, 4, 2.5, 5	4.6 ± 1.67	0.65 ± 0.17
		5	5	5	F	10,000	4, 8, 5, 6, 4	5.4 ± 1.67*	0.52 ± 0.18
	72 h	5	4	4	M	8,000	8, 4, 4, 4	5.0 ± 2.00*	0.70 ± 0.18
		5	5	5	F	10,000	2.5, 6, 4, 5, 3.5	4.2 ± 1.48	0.60 ± 0.43
PA	24 h	5	5	4	M	8,000	5.5, 2.3, 5.5, 3	4.0 ± 1.67	0.79 ± 0.14
(37.50)		5	5	5	F	10,000	8.5, 4.5, 3.5, 3.5, 7.6	5.5 ± 2.37*	0.78 ± 0.16
	48 h	5	5	5	M	10,000	6, 6, 6.5, 8.5, 7	6.8 ± 1.30*	0.85 ± 0.44
		5	5	5	F	10,000	0.5, 3.5, 4.5, 3, 5	3.3 ± 1.75	0.76 ± 0.38
	72 h	5	4	4	M	8,000	2.5, 3, 2.5, 3.5	2.9 ± 0.48	0.54 ± 0.28
		5	5	5	F	10,000	5, 3, 2, 3, 6	3.8 ± 1.64	0.55 ± 0.20
P. Control	24 h	9	9	9	M	18,000	23, 19, 31, 18, 28.19, 34.5, 23, 22.3	24.2 ± 5.76*	0.61 ± 0.22
		7	7	7	F	14,000	33, 16, 18, 13.5, 20, 40, 27.3	24.0 ± 9.78*	0.59 ± 0.19
	48 h	5	5	5	M	10,000	15.5, 17, 13, 9.5, 11.5	13.3 ± 3.01*	0.31 ± 0.06*
		5	5	5	F	10,000	15, 12.5, 6.5, 11, 8	10.6 ± 3.42*	0.39 ± 0.30*

Dose (mg/kg)	Sample time^a	No. of animals			Sex	No. of analyzed PCE	mPCE/1000 PCE (individual data)	Means ± SD	PCE/NCE ± SD
Dose (mg/kg)	Sample time^a	T	S	A	Sex	No. of analyzed PCE	mPCE/1000 PCE (individual data)	Means ± SD	PCE/NCE ± SD
N. Control		9	9	8	M	24,000	3, 3, 1, 3.5, 2.5, 1, 1.5, 0	1.9 ± 1.24	55.20 ± 17.98
		10	10	10	F	25,000	1, 1, 2, 2, 1, 0, 1, 0.5, 1, 1	1.0 ± 0.60	76.20 ± 26.18
PA	24 h	5	5	4	M	8,000	8.6, 4.6, 7.5, 7.5	7.1 ± 1.71*	66.00 ± 42.70
(18.75)		5	5	4	F	6,000	1, 1, 2, 2	1.5 ± 0.58	46.00 ± 12.98*
	48 h	11	11	10	M	17,000	3, 2.5, 2.5, 2, 3, 1, 1, 1, 3, 1	2.0 ± 0.91	53.82 ± 22.71
		10	10	10	F	14,000	1.5, 2.5, 1, 3, 1, 0, 4.2, 1, 1	1.7 ± 1.18	60.38 ± 24.24
	72 h	5	4	4	M	5,000	2, 1, 4, 4	2.3 ± 1.99	61.50 ± 20.61
		5	5	5	F	5,000	2, 2, 1, 1, 1	1.4 ± 0.55	52.60 ± 12.78
	4 d	6	6	6	M	6,000	0, 3, 1, 0, 1, 5	1.7 ± 1.97	75.33 ± 18.99
		5	5	5	F	5,000	4, 1, 1, 3, 4	2.6 ± 1.52*	73.20 ± 22.95
	7 d	6	6	4	M	4,000	1, 0, 1, 0	0.5 ± 0.58	87.80 ± 61.11
		5	5	4	F	4,000	0, 1, 0, 0	0.3 ± 0.50	56.40 ± 12.99
	14 d	6	6	5	M	5,000	4, 4, 2, 1, 1	2.4 ± 1.52	55.20 ± 30.24
		5	5	4	F	4,000	2, 1, 1, 2	1.5 ± 0.58	43.40 ± 28.17
	21 d	6	6	5	M	5,000	0, 0, 1, 0, 0	0.2 ± 0.45	61.17 ± 15.00
		5	5	5	F	5,000	2, 0, 0, 0, 1, 0	0.6 ± 0.89	53.25 ± 2.99
PA	24 h	5	4	4	M	8,000	3.5, 7.5, 1.5, 6.5	4.7 ± 2.92*	41.80 ± 8.66
(37.50)		5	5	5	F	5,000	6, 6, 2, 2, 7	4.6 ± 2.41*	57.80 ± 32.97
	48 h	12	12	10	M	14,000	5.5, 4, 7, 7, 10, 6, 4, 10, 7, 11	7.2 ± 2.47*	46.60 ± 23.86
		11	11	11	F	15,000	2.5, 5, 6, 6.5, 6.5, 7, 12, 4, 5, 5, 1	5.5 ± 2.81*	50.50 ± 13.16
	72 h	5	4	4	M	7,000	4.5, 3.5, 4, 2	3.5 ± 1.27	38.00 ± 10.12
		5	5	5	F	7,000	3, 1, 4, 1.5, 5	2.9 ± 1.67*	45.70 ± 5.86*
	4 d	7	6	6	M	6,000	3, 2, 3, 2, 3, 3	2.7 ± 0.52	99.00 ± 25.18*
		6	6	6	F	5,000	2, 1, 6, 0, 0, 1	1.7 ± 2.25	93.80 ± 12.00
	7 d	7	6	5	M	5,000	1, 0, 2, 5, 6	2.8 ± 2.59	29.00 ± 1.73*
		6	6	4	F	4,000	1, 1, 1, 2	1.3 ± 0.50	37.00 ± 9.86*
	14 d	7	6	5	M	5,000	0, 1, 3, 1, 2	1.4 ± 1.14	63.40 ± 19.76
		6	6	5	F	5,000	1, 4, 3, 2, 1	2.2 ± 1.30	49.20 ± 19.03
	21 d	7	6	5	M	5,000	2, 0, 0, 0, 0	0.4 ± 0.89	63.50 ± 15.72
		6	6	6	F	6,000	0, 0, 0, 0, 1, 0	0.2 ± 0.41	47.80 ± 7.86*
P. Ccontrol	24 h	5	5	5	M	5,000	9, 10, 9, 5, 12	9.0 ± 2.55*
		5	5	5	F	9,000	10, 9, 9, 9.5, 10	9.5 ± 0.50*
	48 h	5	5	5	F	5,000	23, 35, 24, 26, 29	27.5 ± 4.83*	46.20 ± 12.40
		5	5	5	F	5,000	13, 19, 22, 12, 21	17.4 ± 4.62*	37.40 ± 13.26*

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Clastogenic activity of integerrimine determined in mouse micronucleus assays

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