Genotoxic activity of the insecticide Nuvacron (Monocrotophos) detected by the micronucleus test in bone marrow erythrocytes of mice and in CHO cells

Peitl Jr, Paulo; Sakamoto-Nojo, Elza T.; Cólus, Ilce M. de Syllos

doi:10.1590/S0100-84551996000400006

Abstract

The organophosphorus insecticide Nuvacron (Monocrotophos) is a very toxic agent widely utilized in Brazilian agriculture. To evaluate the clastogenic potential of this insecticide, in vivo and in vitro micronucleus (MN) assay experiments were carried out on Swiss mice and on Chinese hamster ovary (CHO) cells, respectively. Nuvacron administered at doses of 2.5 and 5.0 mg/kg induced a statistically significant increase in the frequencies of MN detected in polychromatic bone marrow erythrocytes from animals (six/group) treated ip 24 h before. Exponentially growing CHAO cells were treated continuously (16h) with Nuvacron diluted in water to final concentrations of 1, 10, 100, 200, and 400 mug/ml. Three experiments were carried out using the cytokinesis-block method and a total of 6000 binucleated cells were scored to determine MN frequencies. A statistically significant increase in the frequencies of MN was observed for the cells treated with 1 and 10 mug/ ml Nuvacron. A marked decrease in cell proliferation rates was observed for CHO cultures treated with higher concentrations. These data demonstrate that Nuvacron has a genotoxic effect on both in vivo and in vitro mammalian test systems.

genotoxic; insecticide Nuvacron; micronucleus; bone marrow; erythrocytes; mice; CHO cells

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Genotoxic activity of the insecticide Nuvacron (Monocrotophos) detected by the micronucleus test in bone marrow erythrocytes of mice and in CHO cells

Paulo Peitl Jr.^I,II; Elza T. Sakamoto-Nojo^II,III; Ilce M. de Syllos Cólus^I

^IDepartamento de Biologia Geral, Universidade Estadual de Londrina, Caixa Postal 6001, 86051-970 Londrina, PR, Brasil

^IIDepartamento de Genética e Matemática Aplicada à Biologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, 14049-900 Ribeirão Preto, SP, Brasil

^IIIDepartamento de Biologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, 14040-901 Ribeirão Preto, SP, Brasil. Send correspondence to E.T.S.-H.

ABSTRACT

The organophosphorus insecticide Nuvacron (Monocrotophos) is a very toxic agent widely utilized in Brazilian agriculture. To evaluate the clastogenic potential of this insecticide, in vivo and in vitro micronucleus (MN) assay experiments were carried out on Swiss mice and on Chinese hamster ovary (CHO) cells, respectively. Nuvacron administered at doses of 2.5 and 5.0 mg/kg induced a statistically significant increase in the frequencies of MN detected in polychromatic bone marrow erythrocytes from animals (six/group) treated ip 24 h before. Exponentially growing CHAO cells were treated continuously (16h) with Nuvacron diluted in water to final concentrations of 1, 10, 100, 200, and 400 mg/ml. Three experiments were carried out using the cytokinesis-block method and a total of 6000 binucleated cells were scored to determine MN frequencies. A statistically significant increase in the frequencies of MN was observed for the cells treated with 1 and 10 mg/ ml Nuvacron. A marked decrease in cell proliferation rates was observed for CHO cultures treated with higher concentrations. These data demonstrate that Nuvacron has a genotoxic effect on both in vivo and in vitro mammalian test systems.

Keywords: genotoxic; insecticide Nuvacron; micronucleus; bone marrow; erythrocytes; mice; CHO cells.

References

Adhikari, N. and Grover, I.S. (1988). Genotoxic effects of some systemic pesticides: In vivo chromosomal aberrations in bone marrow cells in rats. Environ. Mol. Mutagen. 12: 235-242.
Bhunya, S.P. and Behera, B.C. (1988). Mutagenicity assay of an organophosphate pesticide, Monocrotophos in a mammalian in vivo test system. Cytologia 53: 801-807.
Bhunya, S.P. and Jena, G.B. (1993). Studies on the genotoxicity of monocrotophos, an organophosphate insecticide, in the chick in vivo test system. Mutat. Res. 292: 231-239.
Cole, R.J., Taylor, N., Cole, J. and Arlett, C.F. (1981). Short-term tests for transplacentally active carcinogens. Micronucleus formation in fetal and maternal mouse erythroblasts. Mutat. Res. 80: 141-157.
De Kergommeaux, D.J., Grant, W.F. and Sandhy, S.S. (1983). Clastogenic and physiological response of chromosomes to nine pesticides in the Vicia faba in vivo root tip assay system. Mutat. Res. 124: 69-84.
Devadas, N., Sadanandam, A., Kishan, R.R. and Subhash, K. (1987). Induced somatic aberration and chlorophyll mutations in Capsicun by insecticides. Cytologia 52: 235-241.
Fenech, M. and Morley, A.A. (1985). Measurement of micronuclei in lymphocytes. Mutat. Res. 147: 29-36.
Grover, I.S. and Malhi, P.K. (1985). Genotoxic effects of some organophosphorous pesticides. I. Induction of micronuclei in bone marrow cells in rat. Mutat. Res. 155: 131-134.
Grover, I.S., Dhingra, K.A., Adhikari, N. and Ladhar, S.S. (1988). Genotoxicity of pesticides. A comparative study using a battery of assays. Nucleus 31: 69-77.
Hayashi, M., Tice, R.R., MacGregor, J.T., Anderson, D., Blakey, D.H., Kirsh-Volders, M., Oleson, F.B., Pacchierotti, F., Romagna, F., Shimada, H., Sutou, S. and Vannier, B. (1994). In vivo rodent erythrocyte micronucleus assay. Mutat. Res. 312: 293-304.
Hoffmann, G.R., Sayer, A.M. and Littlefield, L.G. (1994). Potentiation of bleomicin by the aminothiol WR-1065 in assays for chromosomal damage in Go human lymphocytes. Mutat. Res. 307: 273-283.
Jagetia, G.C. and Ganapathi, N.G. (1994). Radiation-induced micronucleus formation in mouse bone marrow after low dose exposures. Mutat. Res. 304: 235-242.
Jayashree, I.V., Vijayalaxmi, K.K. and Rahiman, M.A. (1994). The genotoxicity of Hirosan, an organophosphorus pesticide in the in vivo mouse. Mutat. Res. 322: 77-85.
Jenssen, D. and Ramel, C. (1978). Factors affecting the induction of micronuclei at low doses of X-rays, MMS and dimethylnitrosamine in mouse erythroblasts. Mutat. Res. 58: 51-65.
Klopman, G., Contreras, R., Rosenkrans, H.S. and Waters, M.D. (1985). Structure-genotoxicity activity relationship of pesticides. Comparison of the results from several short term assays. Mutat. Res. 147: 343-356.
Krishna, G., Kropko, M.L., Ciaravino, V. and Theiss, J.C. (1991). Simultaneous micronucleus and chromosome aberration assessment in the rat. Mutat. Res. 264: 29-35.
Lin, M.F., Wu, C.L. and Wang, T.C. (1987). Pesticide clastogenicity in Chinese hamster ovary cells. Mutat. Res. 188: 241-250.
Moriya, M., Otha, T., Watanabe, K., Miyazawa, K., Kato, K. and Shirasu, Y. (1983). Further mutagenicity studies on pesticides in bacterial reversion assay systems. Mutat. Res. 116: 185-216.
Niraj, K.T. and Patnaik, K.K. (1992).Studies on the genotoxicity of monocrotophos in somatic and germ-line cells of Drosophila. Mu tat. Res. 278: 23-29.
Preston, R.J., Dean, B.D., Galloway, S., Holden, H., McFree, A.F. and Shelby, M. (1987).Analysis of chromosome aberrations in bone marrow cells. Mutat. Res. 189: 157-165.
Rao, B.U.C.B., Sharma, S.R. and Rao, B.G.S. (1987). Cytological effects of organophosphorus insecticides on Allium cepa root meristems. Cytologia 52: 365-371.
Sakamoto-Hojo, E.T., Takahashi, C.S., Ferrari, I. and Motidome, M. (1988). Clastogenic effect of the plant alkaloid ellipticine on bone marrow cells of Wistar rats and on human peripheral blood lymphocytes. Mutat. Res. 199: 11-19.
Savage, J.R.K. (1988).A comment on the quantitative relationship between micronuclei and chromosomal aberrations. Mu tat. Res. 207: 33-36.
Schmid, W. (1975). The micronucleus test. Mutat. Res. 31: 915.
Schmid, W. (1976). The micronucleus test for cytogenetic analysis. In: Chemical Mutagenesis, Principles and Methods for their Detection (Hollaender, A., ed.). Vol. 4. Plenum Press, New York, pp. 31-53.
Shandhu, S.S., Waters, M.D., Simmon, V.F., Mortelmans, K.E., Mitchell, A.D., Jorgenson, T., Jones, D.C.L., Valencia, R. and Stack, F. (1985). Evaluation of the geno-toxic potential of certain pesticides used in Pakistan. In: Basic and Applied Mutagenesis (Muhammed, A. and Von Borstel, R.C., eds.). Plenum Press, New York, pp. 185-219.
Shirasu, Y., Moriya, M., Kato, K., Furuhashi, A. and Kada, T. (1976). Mutagenicity screening of pesticides in the microbial system. Mutat. Res. 40: 19-30.
Sobti, R.C., Krishan, A. and Pfaffenberger, C.D. (1982). Cytokinetic and cytogenetic effects of some agricultural chemicals on human lymphoid cells in vitro: organophosphates. Mutat. Res. 102: 89-102.
Vaidya, V.G. and Patankar, N. (1982). Mutagenic effects of monocrotophos, an insecticide, in mammalian test systems. Indian J. Med. Res. 76: 912-917.
Wang, T.C., Lee, T.C., Lin, M.F. and Lin, S.Y. (1987). Induction of sister-chromatid exchanges by pesticides in primary rat tracheal epithelial cells and Chinese hamster ovary cells. Mutat. Res. 188: 311-321.

Publication Dates

Publication in this collection
27 Oct 2006
Date of issue
1996

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] Adhikari, N. and Grover, I.S. (1988). Genotoxic effects of some systemic pesticides: In vivo chromosomal aberrations in bone marrow cells in rats. Environ. Mol. Mutagen. 12: 235-242.

[2] Bhunya, S.P. and Behera, B.C. (1988). Mutagenicity assay of an organophosphate pesticide, Monocrotophos in a mammalian in vivo test system. Cytologia 53: 801-807.

[3] Bhunya, S.P. and Jena, G.B. (1993). Studies on the genotoxicity of monocrotophos, an organophosphate insecticide, in the chick in vivo test system. Mutat. Res. 292: 231-239.

[4] Cole, R.J., Taylor, N., Cole, J. and Arlett, C.F. (1981). Short-term tests for transplacentally active carcinogens. Micronucleus formation in fetal and maternal mouse erythroblasts. Mutat. Res. 80: 141-157.

[5] De Kergommeaux, D.J., Grant, W.F. and Sandhy, S.S. (1983). Clastogenic and physiological response of chromosomes to nine pesticides in the Vicia faba in vivo root tip assay system. Mutat. Res. 124: 69-84.

[6] Devadas, N., Sadanandam, A., Kishan, R.R. and Subhash, K. (1987). Induced somatic aberration and chlorophyll mutations in Capsicun by insecticides. Cytologia 52: 235-241.

[7] Fenech, M. and Morley, A.A. (1985). Measurement of micronuclei in lymphocytes. Mutat. Res. 147: 29-36.

[8] Grover, I.S. and Malhi, P.K. (1985). Genotoxic effects of some organophosphorous pesticides. I. Induction of micronuclei in bone marrow cells in rat. Mutat. Res. 155: 131-134.

[9] Grover, I.S., Dhingra, K.A., Adhikari, N. and Ladhar, S.S. (1988). Genotoxicity of pesticides. A comparative study using a battery of assays. Nucleus 31: 69-77.

[10] Hayashi, M., Tice, R.R., MacGregor, J.T., Anderson, D., Blakey, D.H., Kirsh-Volders, M., Oleson, F.B., Pacchierotti, F., Romagna, F., Shimada, H., Sutou, S. and Vannier, B. (1994). In vivo rodent erythrocyte micronucleus assay. Mutat. Res. 312: 293-304.

[11] Hoffmann, G.R., Sayer, A.M. and Littlefield, L.G. (1994). Potentiation of bleomicin by the aminothiol WR-1065 in assays for chromosomal damage in Go human lymphocytes. Mutat. Res. 307: 273-283.

[12] Jagetia, G.C. and Ganapathi, N.G. (1994). Radiation-induced micronucleus formation in mouse bone marrow after low dose exposures. Mutat. Res. 304: 235-242.

[13] Jayashree, I.V., Vijayalaxmi, K.K. and Rahiman, M.A. (1994). The genotoxicity of Hirosan, an organophosphorus pesticide in the in vivo mouse. Mutat. Res. 322: 77-85.

[14] Jenssen, D. and Ramel, C. (1978). Factors affecting the induction of micronuclei at low doses of X-rays, MMS and dimethylnitrosamine in mouse erythroblasts. Mutat. Res. 58: 51-65.

[15] Klopman, G., Contreras, R., Rosenkrans, H.S. and Waters, M.D. (1985). Structure-genotoxicity activity relationship of pesticides. Comparison of the results from several short term assays. Mutat. Res. 147: 343-356.

[16] Krishna, G., Kropko, M.L., Ciaravino, V. and Theiss, J.C. (1991). Simultaneous micronucleus and chromosome aberration assessment in the rat. Mutat. Res. 264: 29-35.

[17] Lin, M.F., Wu, C.L. and Wang, T.C. (1987). Pesticide clastogenicity in Chinese hamster ovary cells. Mutat. Res. 188: 241-250.

[18] Moriya, M., Otha, T., Watanabe, K., Miyazawa, K., Kato, K. and Shirasu, Y. (1983). Further mutagenicity studies on pesticides in bacterial reversion assay systems. Mutat. Res. 116: 185-216.

[19] Niraj, K.T. and Patnaik, K.K. (1992).Studies on the genotoxicity of monocrotophos in somatic and germ-line cells of Drosophila. Mu tat. Res. 278: 23-29.

[20] Preston, R.J., Dean, B.D., Galloway, S., Holden, H., McFree, A.F. and Shelby, M. (1987).Analysis of chromosome aberrations in bone marrow cells. Mutat. Res. 189: 157-165.

[21] Rao, B.U.C.B., Sharma, S.R. and Rao, B.G.S. (1987). Cytological effects of organophosphorus insecticides on Allium cepa root meristems. Cytologia 52: 365-371.

[22] Sakamoto-Hojo, E.T., Takahashi, C.S., Ferrari, I. and Motidome, M. (1988). Clastogenic effect of the plant alkaloid ellipticine on bone marrow cells of Wistar rats and on human peripheral blood lymphocytes. Mutat. Res. 199: 11-19.

[23] Savage, J.R.K. (1988).A comment on the quantitative relationship between micronuclei and chromosomal aberrations. Mu tat. Res. 207: 33-36.

[24] Schmid, W. (1975). The micronucleus test. Mutat. Res. 31: 915.

[25] Schmid, W. (1976). The micronucleus test for cytogenetic analysis. In: Chemical Mutagenesis, Principles and Methods for their Detection (Hollaender, A., ed.). Vol. 4. Plenum Press, New York, pp. 31-53.

[26] Shandhu, S.S., Waters, M.D., Simmon, V.F., Mortelmans, K.E., Mitchell, A.D., Jorgenson, T., Jones, D.C.L., Valencia, R. and Stack, F. (1985). Evaluation of the geno-toxic potential of certain pesticides used in Pakistan. In: Basic and Applied Mutagenesis (Muhammed, A. and Von Borstel, R.C., eds.). Plenum Press, New York, pp. 185-219.

[27] Shirasu, Y., Moriya, M., Kato, K., Furuhashi, A. and Kada, T. (1976). Mutagenicity screening of pesticides in the microbial system. Mutat. Res. 40: 19-30.

[28] Sobti, R.C., Krishan, A. and Pfaffenberger, C.D. (1982). Cytokinetic and cytogenetic effects of some agricultural chemicals on human lymphoid cells in vitro: organophosphates. Mutat. Res. 102: 89-102.

[29] Vaidya, V.G. and Patankar, N. (1982). Mutagenic effects of monocrotophos, an insecticide, in mammalian test systems. Indian J. Med. Res. 76: 912-917.

[30] Wang, T.C., Lee, T.C., Lin, M.F. and Lin, S.Y. (1987). Induction of sister-chromatid exchanges by pesticides in primary rat tracheal epithelial cells and Chinese hamster ovary cells. Mutat. Res. 188: 311-321.