AUCTORES
Globalize your Research
Research Article | DOI: https://doi.org/10.31579/2642-9799/011
Preclinical Development, Bangalore, India
*Corresponding Author: Shiva kumar M, Preclinical Development, Bangalore, India; E-mail: Mshivakumar@gmail.com
Citation: Shiva kumar M, Significant increase in the dominant lethal mutations: benzo(a)pyrene, J Biomarkers and Drug Discovery. Doi: 10.31579/2642-9799/011
Copyright: © Shiva kumar M. This is an open-access article distributed under the terms of The Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 06 November 2018 | Accepted: 19 November 2018 | Published: 29 November 2018
Keywords: Turmeric; benzo(a)pyrene; mutations; dominant lethal assay
Background: Use of biomarkers particularly under in vivo condition is of importance in risk assessment. This study is proposed to identify the in vivo antigenotoxic potential using dominant lethal mutation test in B(a)P exposed, turmeric fed animals and evaluate the role of turmeric in counteracting the germ cell mutations.
Methods: Twenty four male mice were taken and divided into 4 groups each group containing 6 mice/group. The first and second group received stock diet (control) while the third and fourth groups received 5% turmeric diet for a period of one month. At the end of feeding period, second and fourth group received a single dose of benzo(a)pyrene 1mg/mouse intraperitoneally. After 1 week each male mouse was mated to 3 female mice at 1,4, 8 and 12 week intervals. On 13th day from mid point of mating, the females were sacrificed and live and dead embryos were counted to study the pre and post implantation loss of embryos. The differences in the frequencies of pre and post implant deaths were done by comparing treated with control group at 4-time periods by analysis of variance (ANOVA) and chi-square test which is used to compare treatment group and positive control with negative control.
Results: Feeding of 5% turmeric and treatment with a single dose of B(a)P did not show any significant effect on the mutagenic index or the frequency of pregnancy in treated groups compared with control. There was no apparent induction of dominant lethal mutations in B(a)P or B(a)P+Turmeric treated groups. No post implantation dominant lethal effects produced by B(a)P could be detected in this study. The induction of B(a)P and treatment with turmeric did not influence the dominant lethal test.
Conclusion: B(a)P did not produce a significant increase in the dominant lethal mutations. Turmeric also did not give any positive response and may be considered as non-mutagenic. The negative result suggests that under the conditions of the test the test substance may not be genotoxic in the germ cell of the treated sex of the test species.
DNA damage is a common feature of human spermatozoa with purported links to poor rates of conception, impaired embryonic development and increased incidence of miscarriage and the appearance of various kinds of morbidity in the offspring. Reactive oxygen species from various chemical carcinogens are known to play an important role in cell damage and in the development of cancer. Many free radical scavengers which are naturally occurring antioxidants have been found to be effective in inhibiting the induction of carcinogenesis by a wide variety of chemical carcinogens like benzo(a)pyrene (B(a)P) which is a polycyclic aromatic hydrocarbon (PAH) and these hydrocarbons are mutagenic in somatic cells [1]. B(a)P is metabolized into BP diol epoxide that is able to bind to DNA and form bulky DNA adducts. Many studies have indicated that various spice principles are rich in anti oxidants. Turmeric belonging to the family zingiberaceae is used in Indian culinary and is an important spice crop having many medicinal properties. It is known that dietary substances like turmeric may also inhibit the genotoxic potential of some chemical carcinogens [2]. In addition a careful evaluation of possible toxicological and gentoxicological consequences for human health transplacental and transgeneration effects is necessary as humans will be largely exposed to potent inhibitors of carcinogenesis [3]. In particular it may be of much interest to evaluate the effect of turmeric towards B(a)P toxicity. This study is proposed to identify the in vivo antigenotoxic potential using dominant lethal mutation test in B(a)P exposed, turmeric fed animals and evaluate the role of turmeric in counteracting the germ cell mutations.
Materials and methods
Male and female Albino Swiss mice were obtained from the National Centre for Laboratory Animal Science (NCLAS) located in National Institute of Nutrition, Hyderabad and housed in the animal facility where the temperature was maintained at 24- 25°C with 12h dark/light cycle. The experimental protocol was approved by the Institutional Animal Ethics Committee (IAEC) under the Committee for Purpose of Control and Supervision on Experiments on Animals (CPCSEA), Ministry of Environment and Forests, Government of India. Turmeric powder was obtained from commercially available standard grade (AGMARK).
Study design
Twenty four male mice were taken and divided into 4 groups each group containing 6 mice/group. The first and second group received stock diet (control) while the third and fourth groups received 5% turmeric diet for a period of one month. At the end of feeding period, second and fourth group received a single dose of benzo(a)pyrene 1mg/mouse intraperitoneally . After 1 week each male mouse was mated to 3 female mice at 1, 4, 8 and 12e week intervals. On 13th day from mid point of mating, the females were sacrificed and live and dead embryos were counted to study the pre and post implantation loss of embryos. These studies were conducted in 6males and 18 females. The same males were used for mating throughout experiment.
Dominant lethal assay
Male mice were exposed to B (a)P and were mated to untreated virgin female mice. The various germ cell stages were tested by the use of sequential mating intervals. The females were sacrificed after an appropriate period of time, and the contents of uteri were examined to determine the number of implants and live and dead embryos. The calculation of dominant lethal effect was based on comparison of the live implants per female in the treated group to the live implants per female in the control group. The increase of dead implants per female in the treated group over the dead implants per female in the control group reflected the post implantation loss. The post implantation loss was calculated by determining the ratio of dead to total implants from the treated group compared to the ratio of dead to total implants from the control group. Pre implantation loss was estimated on the basis of comparing the total implants per female in treated and control groups.
Statistical analysis
The differences in the frequencies of pre and post implant deaths were done by comparing treated with control group at 4-time period by analysis of variance (ANOVA) and chi-square test which is used to compare treatment group and positive control with negative control. The total number of implantations is evaluated by the Student's t-test to determine whether the average number of implantations per pregnant female for each treatment group and the positive control group differs significantly from the negative control group. Mutagenic effects were expressed conventionally as the mutagenic index (fetal deaths/total implants) X100.
The statistical evaluations were based on the control values for each mating period. The results were tested to ascertain whether there was any dominant lethal effect. The dominant lethal effect in the experimental groups was calculated from the average number of live embryos obtained from the pregnant females as percentage of control. The numbers of living and dead implants were analyzed by chi-square test and to verify these results t-test was performed in which the rates of living implants in the control and treated groups were compared with one another. Frequency of pregnancy is represented in (Table 1 and 2), and was found to be not significant. No post-implantation dominant lethal effects produced by B(a)P could be detected in this study. The fraction of dead embryos was not significantly different from control groups (Table 3). No significant pre-implantation losses were noted in either B(a) P or B(a)P+5%turmeric treated groups compared to control . The mutagenic index compared between control versus turmeric and other B(a)P treated groups was not significant as analyzed by t-test.
The dominant lethal test in male is intended to detect mutagenic effects in the spermatogenic process that are lethal to embryos or fetus [5]. B(a)P has been shown to cause genotoxic effects in a broad range of prokaryotic and mammalian cell systems [6]. This study was taken up to evaluate dominant lethal mutation effects of turmeric in mice treated with a single dose of B(a)P 1mg/mouse. Extensive research has been carried out in NIN on turmeric, ginger, garlic etc. and has been demonstrated their antimutagenic effect using in vivo rat model [7,8]. Earlier reports showed that turmeric did not induce sex-chromosome loss and dominant lethal mutation did not occur when hot water extracts were administered to male drosophila [9]. A multigenerational study was conducted according to OECD testing guidelines using curcumin comprising 80%. The authors reported that there were no treatment related clinical signs of toxicity or mortality during the premating period and there were no differences in gestational or post partum body weights in either generation. Curcumin was reportedly non-carcinogenic over three generations [10]. Govindarajan [11] reported that administration of curcumin into rats and rabbits at doses of 600 or 1600 mg/kg body weight did not show any effect on total implants, resorption, live and dead embryos and rats fed diet containing 0.5% turmeric or 0.015% curcumin for 12 weeks did not have any adverse effect on pregnancy rate, mean number of live and dead embryos. In another study incorporation of 0.5% turmeric or 0.015% curcumin in diets of mice did not show significant differences on the incidence of micronucleated PCE's, pregnancy rates and number of live and dead embryos, total implants and mutagenic index [12]. Other studies conducted on antimutagenicity of turmeric for a period of three months on 1, 3 and 5% turmeric in the diet and which received B(a)P on three occasions did not show any significant changes in any of the organs [13]. In one study multigenerational reproductive toxicity indicated that turmeric consumed at 500mg/kg body weight or an alcoholic extract at 60mg/Kg body weight per day did not affect the fertility index, gestational and lactation index and no abnormal histological changes were recorded [14].
In this study feeding of 5% turmeric and treatment with a single dose of B(a)P did not show any significant effect on the mutagenic index or the frequency of pregnancy in treated groups compared to control. There was no apparent induction of dominant lethal mutations in B(a)P or B(a)P+ Turmeric treated groups. No post implantation dominant lethal effects produced by B(a)P could be detected in this study. The induction of B(a)P and treatment with turmeric did not influence the dominant lethal test.
B(a)P did not produce a significant increase in the dominant lethal mutations. Turmeric also did not give any positive response and may be considered as non-mutagenic. The negative result suggests that under the conditions of the test the test substance may not be genotoxic in the germ cell of the treated sex of the test species.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
