Pesticide Roundup Provokes Cell Division Dysfunction at the Level of CDK1/Cyclin B Activation

Abstract

To assess human health risk from environmental chemicals, we have studied the effect on cell cycle regulation of the widely used glyphosate-containing pesticide Roundup. As a model system we have used sea urchin embryonic first divisions following fertilization, which are appropriate for the study of universal cell cycle regulation without interference with transcription. We show that 0.8% Roundup (containing 8 mM glyphosate) induces a delay in the kinetic of the first cell cleavage of sea urchin embryos. The delay is dependent on the concentration of Roundup. The delay in the cell cycle could be induced using increasing glyphosate concentrations (1-10 mM) in the presence of a subthreshold concentration of Roundup 0.2%, while glyphosate alone was ineffective, thus indicating synergy between glyphosate and Roundup formulation products. The effect of Roundup was not lethal and involved a delay in entry into M-phase of the cell cycle, as judged cytologically. Since CDK1/cyclin B regulates universally the M-phase of the cell cycle, we analyzed CDK1/cyclin B activation during the first division of early development. Roundup delayed the activation of CDK1/cyclin B in vivo. Roundup inhibited also the global protein synthetic rate without preventing the accumulation of cyclin B. In summary, Roundup affects cell cycle regulation by delaying activation of the CDK1/cyclin B complex, by synergic effect of glyphosate and formulation products. Considering the universality among species of the CDK1/cyclin B regulator, our results question the safety of glyphosate and Roundup on human health.

Ultrastructural analysis of testes from mice fed on genetically modified soybean

“…Consistent with this hypothesis, traces of glyphosate have actually been detected in milling and bread from treated GM-soybean (Granby et al 2003). Although a direct evidence does not exist for an effect of glyphosate on transcription and translation, it has been shown that it generates DNA adducts (when used at high doses: Peluso et al, 1998) and cell division dysfunction (when administered at low doses, Marc et al, 2002).The presence of residual glyphosate could also account for the presence of SER enlargements in Sertoli cells: in fact, Walsh et al (2000) reported that glyphosate affects SER-related steroidogenesis through the disruption of StAR protein expression. …”

Re-registration Challenges of Glyphosate in the European Union

“…Roundup Original R was found cytotoxic to human adipose-derived mesenchymal stem cells with an IC 50 value corresponding to glyphosate concentration of 43.0 ± 1.7 µg/ml, induced death by apoptosis and necrosis upon 24 h of exposure, and caused reduced alkaline phosphatase activity in cells induced to osteogenic differentiation (de Melo et al, 2018). Formulations containing glyphosate IPA salt, Roundup 3 Plus R , Roundup Biovert R , Amega R , Cargly R and Cosmic R , unlike glyphosate alone, were shown to affect cell proliferation in embryonic cells 360 min upon fertilization of the sea urchin Sphaerechinus granularis inducing a delay in entry into the Mphase in the cell cycle (Marc et al, 2002(Marc et al, , 2004. A Roundup R formulation, but again not glyphosate, was shown to affect cell proliferation and steroid production, as dramatically decreased cell numbers, as well as estradiol and progesterone production were recorded in granulosa cells from beef heifer ovaries upon exposure to Roundup R at 0.01-0.30 mg/ml (corresponding to glyphosate concentrations of 0.0018-0.054 mg/ml) (Perego et al, 2017).…”

Acute toxicity and histopathological alterations of Roundup® herbicide on "cachama blanca" (Piaractus brachypomus)

“…These components can gain access to the central nervous system through the olfactory epithelium and then to the olfactory bulb in the telencephalon, this could agree with the focalization of degenerative neuronal processes to the olfactory bulb, and/ or through the blood/brain barrier where the surfactant components because of their amphiphylic character and incorporation into biological membranes could facilitate access of GP and its own passage (Stock & Holloway 1993). Predisposition of the olfactory bulb to degenerative foci could be generated by its communication with the olfactory epithelium and/or by the presence of proliferation centers and neural regeneration (Lema et al 2005) where Roundup ® components might induce alterations in the control points of the cellular cycle or in transcription processes that occur during neurogenesis (Marc et al 2002(Marc et al , 2003(Marc et al , 2004a(Marc et al ,b, 2005. The EGC/MC present in meninges and in the telencephalon cortex follow a pattern of satellitosis around neurons with degenerative foci, possibly triggering or accelerating apoptosis ( Fig.10-11).…”