Carcinogenesis with the insecticide rotenone

doi:10.1016/0024-3205(83)90216-3

Life Sciences

Volume 32, Issue 8, 21 February 1983, Pages 809-816

https://doi.org/10.1016/0024-3205(83)90216-3 Get rights and content

Abstract

Rotenone is an insecticide which has been used extensively for a long time, and is now widely used in the U.S.A. and other industrialized countries. Rotenone is used mainly as an agricultural insecticide, household garden insecticide and water plant piscicide. Through these uses, rotenone may now be reaching the human male and female in these countries in substancial amounts, carried by fresh or cooked vegetables, consumed fish and drinking water. A review of the existing published reports and unpublished official documents dealing with the capacity of rotenone to induce neoplastic, paraneoplastic and preneoplastic lesions in the rat is presented here. It is strongly suggested that rotenone is carcinogenic to the rat (at doses from 2 to 25 parts per million continuously in food, or from 0.8 to 2.5 mg/kg weight for 1 to 4 months by oral administration), above all, when the rats receive deficient diets, especially those poor in riboflavin. Rotenone carcinogenesis, among other things, seems to exhibit a peculiar dose response pattern, which could be explained by its possible hormonal mechanism of action. Further studies to assess definitively the role of rotenone as a possible environmental carcinogen are proposed as being highly necessary.

References (32)

M.J. Figueras et al.
Eur. J. Cancer
(1973)
M. Gosalvez et al.
Eur. J. Cancer
(1978)
W.H. Hansen et al.
Toxicology and Applied Pharmacology
(1965)
T.J. Haley
J. Environmen. Pathol. and Toxicol.
(1978)
F.B. Laforge et al.
Chem. Rev.
(1933)
M. Miyano
J. Am. Chem. Soc.
(1965)
K.E. Oberg
Exptl. Cell Res.
(1961)
J. Fukami et al.
Science
(1967)
W.D. Watkins et al.
O. Gaudin et al.
Bull. Sci. Pharmacol.
(1938)

R. Santi et al.

Farmaco. Ed. Sci.

(1965)

J. Racouchot

Arch. Ma. Profes.

(1939)

E. Geoffrey

Ann. Inst. Colon. Marseilles

(1895)

M. Ono

Oyo-Kontyu

(1941)

H.M. Cheng et al.

J. Agr. Food Chem.

(1972)

R. Schnick

A Review of the Literature on the Use of Rotenone in Fisheries

(1974)

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Estrogenic flavonoids and their molecular mechanisms of action
2023, Journal of Nutritional Biochemistry
Citation Excerpt :
Rotenone has been widely used for many years as a pesticide for animals and agricultural plants, and a piscicide for fisheries management [459]. Retenone was reported to be carcinogenic [460]. Recently, it has become clear that rotenone exhibits other activities; rotenone treatment resulted in etiopathogenesis of Parkinson's disease in a rat model [459]; rotenone induces micronuclei and modifies the function of microtubule organizing centers [461]; rotenone impaired neuronal polarization in neurons by affecting the stability of microtubules and actin cytoskeleton by regulating small GTPase RhoA [462].
Flavonoids are a major group of phytoestrogens associated with physiological effects, and ecological and social impacts. Although the estrogenic activity of flavonoids was reported by researchers in the fields of medical, environmental and food studies, their molecular mechanisms of action have not been comprehensively reviewed. The estrogenic activity of the respective classes of flavonoids, anthocyanidins/anthocyanins, 2-arylbenzofurans/3-arylcoumarins/α-methyldeoxybenzoins, aurones/chalcones/dihydrochalcones, coumaronochromones, coumestans, flavans/flavan-3-ols/flavan-4-ols, flavanones/dihydroflavonols, flavones/flavonols, homoisoflavonoids, isoflavans, isoflavanones, isoflavenes, isoflavones, neoflavonoids, oligoflavonoids, pterocarpans/pterocarpenes, and rotenone/rotenoids, was summarized through a comprehensive literature search, and their structure-activity relationship, biological activities, signaling pathways, and applications were discussed. Although the respective classes of flavonoids contained at least one chemical mimicking estrogen, the mechanisms varied, such as those with estrogenic, anti-estrogenic, non-estrogenic, and biphasic activities, and additional activities through crosstalk/bypassing, which exert biological activities through cell signaling pathways. Such mechanistic variations of estrogen action are not limited to flavonoids and are observed among other broad categories of chemicals, thus this group of chemicals can be termed as the “estrogenome”. This review article focuses on the connection of estrogen action mainly between the outer and the inner environments, which represent variations of chemicals and biological activities/signaling pathways, respectively, and form the basis to understand their applications. The applications of chemicals will markedly progress due to emerging technologies, such as artificial intelligence for precision medicine, which is also true of the study of the estrogenome including estrogenic flavonoids.
Induction of apoptotic erythrocyte death by rotenone
2012, Toxicology
Citation Excerpt :
Rotenone is toxic to neurons (Hirata et al., 2008; Hirata and Nagatsu, 2005; Kim et al., 2009; Swarnkar et al., 2010) and rotenone treatment of animals is a widely used model of Parkinson's disease (Duty and Jenner, 2011; Greenamyre et al., 2010; Nistico et al., 2011; Reiter et al., 2010). Rotenone has further been implicated in the pathogenesis of malignancy (Gosalvez, 1983). On the other hand, rotenone administration may overcome multidrug resistance of tumor cells (Molnar et al., 2010).
The pesticide rotenone stimulates apoptosis and rotenone intoxication has been considered a cause of Parkinson's disease. Rotenone further sensitizes tumor cells to cytotoxic drugs. The apoptotic effect of rotenone is at least partially due to mitochondrial injury. Even though lacking mitochondria and nuclei, erythrocytes may undergo eryptosis, an apoptosis-like suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine-exposure at the cell surface. Triggers of eryptosis include increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i) and enhanced ceramide formation. The present study explored, whether rotenone elicits eryptosis. To this end, [Ca²⁺]_i was estimated utilizing Fluo3-fluorescence, cell volume from forward scatter, phosphatidylserine-exposure from annexin-V-binding, ceramide utilizing fluorescence antibodies and hemolysis from hemoglobin release. A 48 h exposure to rotenone significantly increased Fluo3-fluorescence_i (≥1 μM), increased ceramide abundance (10 μM), decreased forward scatter (≥2.5 μM) and increased annexin-V-binding (≥ 1 μM). Rotenone exposure was further followed by slight but significant hemolysis. Rotenone-induced cell membrane scrambling was significantly blunted, but not completely abrogated by removal of extracellular Ca²⁺. The present observations disclose a novel effect of rotenone, i.e. triggering of erythrocyte shrinkage and cell membrane scrambling, an effect paralleled by and partially dependent on Ca²⁺-entry.
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Determination of rotenone residues in foodstuffs by solid-phase extraction (SPE) and liquid chromatography/tandem mass spectrometry (LC-MS/MS)
2010, Agricultural Sciences in China
We developed a novel approach to determine rotenone residues in foodstuffs, by integrating solid-phase extraction (SPE) and liquid chromatography/tandem mass spectrometry (LC-MS/MS) technologies, to achieve high sensitivity and selectivity. In our method, the solvent extraction with n-hexane-dichloromethane (50:50, v/v) and cleanup with florisil SPE cartridges using ethyl acetate-ethyl ether (25:75, v/v) as eluents provided adequate recovery of rotenone. The detection of rotenone was then carried out by LC-MS/MS using acetonitrile-water with the 0.1% formic acid (w/v) as the mobile phase. The multiple reaction monitoring (MRM) scheme employed in the approach involved the transitions of the precursor ion to three selected product ions, in which one pair for quantification was m/z 395.3 > 213.2 and the other two pairs for identification were m/z 395.3 > 192.2 and 395.3 > 367.0. The limits of quantification (LOQs) of the method ranged from 0.001 to 0.005 mg kg⁻¹ depending on the matrix. Intra- and inter-day precisions (relative standard deviations, RSDs) for rotenone were less than 7.1 and 14.8%, respectively. Results from repetitive analysis suggested good reproducibility of the method for rotenone residue detection. The recoveries at three concentrations (LOQ, 10LOQ and 100LOQ) ranged from 79.3-118.3% in cabbage, potato, onion, carrot, apple, orange, banana, lichee, tea, and Shiitake mushroom. The proposed procedure was then applied to the analysis of 129 real samples collected from Xiamen, Fujian Province, China. The existence of rotenone was found in two tea products with concentrations of 0.012 and 0.016 mg kg⁻¹, respectively. The method has great potential for routine analysis of monitoring rotenone residue in foodstuffs.
Pest Control Agents from Natural Products
2010, Hayes' Handbook of Pesticide Toxicology
This chapter explores natural pest control agents of practical or historical importance. Natural products have been used to control animal pests, plant diseases, and weeds since ancient times. The biological activity spectrum of natural pesticides is extremely variable, and the selectivity is often achieved by targeted application, often relying on the behavior of the target pest. However, the biological property of a chemical is a function of its structure rather than its origin. The biological activity exerted by a given dose of the compound under given circumstances, especially as related to safety, depends on the way in which the chemical is used. Natural substances used for pest and disease control are generally nonpersistent under field conditions. Most of these often-complex molecules are readily transformed abiotically by light and/or oxygen into less toxic products. There are many natural insect control agents, most of which were discovered by empirical screening of plants and, recently, other natural sources. Moreover, research on insect physiology and behavior made possible the commercialization of chemicals that can be used to manipulate insect development or behavior.

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MinireviewCarcinogenesis with the insecticide rotenone

Abstract

Eur. J. Cancer

Eur. J. Cancer

Toxicology and Applied Pharmacology

J. Environmen. Pathol. and Toxicol.

Chem. Rev.

J. Am. Chem. Soc.

Exptl. Cell Res.

Science

Bull. Sci. Pharmacol.