Effects of N-Nitrosodiethylamine, a Potent Carcinogen, on Sexual Development, Gametogenesis, and Oocyte Maturation

U, Reshma Nair; Victor, Anju C.; Paul, Vinod; Paul‐Prasanth, Bindhu

doi:10.1159/000477106

Cited by 4 publications

(6 citation statements)

References 33 publications

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“…Cordycepin is known to affect the cell cycle in oocytes and early embryos, presumably through its well-characterised effects on the cytoplasmic polyadenylation of mRNAs encoding cell cycle regulators [ 45 ]. Indeed, we found 15 papers confirming these effects on vertebrate oocyte maturation and embryonic cell division [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ].…”

Section: Resultsmentioning

confidence: 66%

“…Cordycepin is known to affect the cell cycle in oocytes and early embryos, presumably through its well-characterised effects on the cytoplasmic polyadenylation of mRNAs encoding cell cycle regulators [45]. Indeed, we found 15 papers confirming these effects on vertebrate oocyte maturation and embryonic cell division [46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61]. The role of cytoplasmic polyadenylation in normal mitotic cell division is, however, less clear [60,62].…”

Section: Cell Death Survival and Divisionmentioning

confidence: 54%

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A Systematic Review of the Biological Effects of Cordycepin

Radhi

Ashraf²,

Lawrence

et al. 2021

Molecules

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We conducted a systematic review of the literature on the effects of cordycepin on cell survival and proliferation, inflammation, signal transduction and animal models. A total of 1204 publications on cordycepin were found by the cut-off date of 1 February 2021. After application of the exclusion criteria, 791 papers remained. These were read and data on the chosen subjects were extracted. We found 192 papers on the effects of cordycepin on cell survival and proliferation and calculated a median inhibitory concentration (IC50) of 135 µM. Cordycepin consistently repressed cell migration (26 papers) and cellular inflammation (53 papers). Evaluation of 76 papers on signal transduction indicated consistently reduced PI3K/mTOR/AKT and ERK signalling and activation of AMPK. In contrast, the effects of cordycepin on the p38 and Jun kinases were variable, as were the effects on cell cycle arrest (53 papers), suggesting these are cell-specific responses. The examination of 150 animal studies indicated that purified cordycepin has many potential therapeutic effects, including the reduction of tumour growth (37 papers), repression of pain and inflammation (9 papers), protecting brain function (11 papers), improvement of respiratory and cardiac conditions (8 and 19 papers) and amelioration of metabolic disorders (8 papers). Nearly all these data are consistent with cordycepin mediating its therapeutic effects through activating AMPK, inhibiting PI3K/mTOR/AKT and repressing the inflammatory response. We conclude that cordycepin has excellent potential as a lead for drug development, especially for age-related diseases. In addition, we discuss the remaining issues around the mechanism of action, toxicity and biodistribution of cordycepin.

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Section: Resultsmentioning

confidence: 66%

“…Cordycepin is known to affect the cell cycle in oocytes and early embryos, presumably through its well-characterised effects on the cytoplasmic polyadenylation of mRNAs encoding cell cycle regulators [45]. Indeed, we found 15 papers confirming these effects on vertebrate oocyte maturation and embryonic cell division [46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61]. The role of cytoplasmic polyadenylation in normal mitotic cell division is, however, less clear [60,62].…”

Section: Cell Death Survival and Divisionmentioning

confidence: 54%

A Systematic Review of the Biological Effects of Cordycepin

Radhi

Ashraf²,

Lawrence

et al. 2021

Molecules

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“…Unlike other organ systems, gonadal development is quite a lengthy process in vertebrates including humans and gets completed only at puberty, which takes several months to years depending on the species. During the early stages of gonadal development, most of the germ cells are undifferentiated and any adverse effect at this stage could hamper its differentiation process, ultimately resulting in various health hazards including cancers of the reproductive organs and infertility in both men and women and other species. , Similar to mammals, medaka is a gonochorist, from which the male and female gonads could be clearly distinguished at the time of birth by looking at the morphological features of the developing gonads . Additionally, using Qurt strain of medaka was advantageous for this study as sexual genotype of the embryos could be identified with the help of sex-linked phenotypic markers (leucophores) from 3 dpf.…”

Section: Resultsmentioning

confidence: 99%

“…Such studies are essential as several engineered nanoparticles (ENPs) were shown to affect reproduction through their toxic effects on gametes, which are responsible for transmission of genetic material across generations and thus, aid in the propagation of various species. Emerging data have revealed the alarming sensitivity of early stages of germ cell development to various exogenous factors. , Germ cell proliferation and meiosis are vital for the differentiation and genesis of gametes, the sperms and the ova. Hence, damages incurred to germ cells during early development could result in developmental and functional anomalies of reproductive organs that could get manifested only in adulthood.…”

Section: Introductionmentioning

confidence: 99%

“…Emerging data have revealed the alarming sensitivity of early stages of germ cell development to various exogenous factors. 23,24 Germ cell proliferation and meiosis are vital for the differentiation and genesis of gametes, the sperms and the ova. Hence, damages incurred to germ cells during early development could result in developmental and functional anomalies of reproductive organs that could get manifested only in adulthood.…”

Section: Introductionmentioning

confidence: 99%

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Graphene Quantum Dots Alter Proliferation and Meiosis of Germ Cells Only in Genetic Females of Japanese Medaka during Early Embryonic Development

Krishnakumar

Paul

Ariyath

et al. 2019

ACS Appl. Bio Mater.

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Graphene quantum dots (GQDs) have emerged as promising biolabeling agents owing to their stable innate fluorescence, photostability, and biocompatibility as opposed to semiconductor quantum dots. While several studies reported GQDs to be cytocompatible, their potential for reproductive toxicity, particularly to germ cells that can cause transgenerational toxicity, remains unexplored. Here we report the intrinsic toxicity of 2–3 nm sized GQDs synthesized from glucose by a novel bottom-up green chemistry technique on germ cell proliferation and meiosis during early embryonic development. In vitro cell viability studies with a normal ovarian cell line, Chinese Hamster Ovarian cells (CHO), and a primary cell type, Human Umbilical Vein Endothelial Cells (HUVEC), portrayed good cytocompatibility even up to a high concentration of 800 μg/mL. When embryos of Japanese medaka were exposed to GQDs, no developmental toxicity was observed up to 250 μg/mL, beyond which hatchability and survival were affected adversely. In contrast, toxicity to germ cells in developing gonads was apparent in genetically female (XX) embryos exposed to much lower doses (50, 75, and 100 μg/mL), at which in vitro cytotoxicity and embryo hatchability and survival were unaffected. A drastic decline in germ cell number and meiosis was observed at these doses in XX embryos implying anomalies in sexual differentiation of the gametes. Conversely, germ cells of genetically male embryos exposed to GQDs were unaltered. Significantly high levels of reactive oxygen species (ROS) were detected in the XX larvae exposed to GQDs; however, there was no DNA damage, suggesting ROS to be responsible for the adverse effects observed.

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A systematic review on multipotent carcinogenic agent, N‐nitrosodiethylamine (NDEA), its major risk assessment, and precautions

Janmeda,

Jain,

Chaudhary

et al. 2024

J of Applied Toxicology

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The International Agency for Research on Cancer has classified N‐nitrosodiethylamine (NDEA) as a possible carcinogen and mutagenic substances, placing it in category 2A of compounds that are probably harmful to humans. It is found in nature and tobacco smoke, along with its precursors, and is also synthesized endogenously in the human body. The oral or parenteral administration of a minimal quantity of NDEA results in severe liver and kidney organ damage. The NDEA required bioactivation by CYP450 enzyme to form DNA adduct in the alkylation mechanism. Thus, this bioactivation directs oxidative stress and injury to cells due to the higher formation of reactive oxygen species and alters antioxidant system in tissues, whereas free radical scavengers guard the membranes from NDEA‐directed injury in many enzymes. This might be one of the reasons in the etiology of cancer that is not limited to a certain target organ but can affect various organs and organ systems. Although there are various possible approaches for the treatment of NDEA‐induced cancer, their therapeutic outcomes are still very dismal. However, several precautions were considered to be taken during handling or working with NDEA, as it considered being the best way to lower down the occurrence of NDEA‐directed cancers. The present review was designed to enlighten the general guidelines for working with NDEA, possible mechanism, to alter the antioxidant line to cause malignancy in different parts of animal body along with its protective agents. Thus, revelation to constant, unpredictable stress situations even in common life may remarkably augment the toxic potential through the rise in the oxidative stress and damage of DNA.

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Effects of N-Nitrosodiethylamine, a Potent Carcinogen, on Sexual Development, Gametogenesis, and Oocyte Maturation

Cited by 4 publications

References 33 publications

A Systematic Review of the Biological Effects of Cordycepin

A Systematic Review of the Biological Effects of Cordycepin

Graphene Quantum Dots Alter Proliferation and Meiosis of Germ Cells Only in Genetic Females of Japanese Medaka during Early Embryonic Development

A systematic review on multipotent carcinogenic agent, N‐nitrosodiethylamine (NDEA), its major risk assessment, and precautions

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