{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:10:23Z","timestamp":1780467023087,"version":"3.54.1"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,2,26]],"date-time":"2023-02-26T00:00:00Z","timestamp":1677369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["RSP2023R502"],"award-info":[{"award-number":["RSP2023R502"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Polypropylene is a thermoplastic polymer playing the role of an endocrine disruptor that interferes with the union, emission, transport or elimination of normal hormones. Epidemiological information indicated the relation of endocrine\u2010disturbing chemicals with prostate cancer, testis tumor and diminished fertility. <jats:italic>p53<\/jats:italic> is a key tumor silencer gene. The present study aimed to evaluate luteinizing hormone (LH) and follicle\u2010stimulating hormone (FSH) levels and the risk of <jats:italic>p53<\/jats:italic> mutations as a result of exposure to polypropylene in non\u2010tumorous adult male factory workers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In total, 150 (controls\u2009=\u200935, workers\u2009=\u2009115) subjects were recruited. Groups were maintained according to the tenure of exposure G1 (1\u20135\u2009years), G2 (6\u201310\u00a0years), G3 (11\u201315\u2009years) and G4 (16\u201320\u2009years). Concentrations of LH and FSH were determined through an enzyme\u2010linked immunosorbent assay. Genotyping analysis was performed by polymerase chain reaction based gel electrophoresis followed by DNA sequencing. The structural and functional impact of the mutation on the p53 structure was evaluated using 50\u2010ns molecular dynamics (MD) simulations and protein\u2010DNA docking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mean plasma LH levels were significantly decreased in G1 (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05) as well as the G2, G3 and G4 (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.001) groups. Similarly, FSH levels were significant decrease in G1 (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05), G2 (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.01), G3 (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.001) and G4 (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.001) compared to the control group. Sequencing results found three variants i.e. g.13450\u2009T&gt;G, g.13430C&gt;T and g.13737G&gt;A. One of them was predicted to be disease\u2010causing others are polymorphisms. MD simulation of missense mutation R273H showed no structural impact on the protein structure in MD simulation, but it resulted in weaker binding of p53 with the DNA that might lower the gene expression of cell cycle regulatory proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings predict decreased fertility and risk of malignancies in the future. The spectrum of <jats:italic>p53<\/jats:italic> mutations as a result of polypropylene exposure in the Pakistani population has not been investigated before. Further studies and meta\u2010analyses are required to elucidate the role of different plasticizers in reproduction and cancer\u2010causing risk factors in a larger population.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3483","type":"journal-article","created":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T08:48:28Z","timestamp":1676364508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mutation pattern of cancer suppressor <i>p53<\/i> gene in factory workers exposed to polypropylene and impact on their reproductive hormones"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2167-8630","authenticated-orcid":false,"given":"Suhail","family":"Razak","sequence":"first","affiliation":[{"name":"Department of Community Health Sciences, College of Applied Medical Sciences King Saud University Riyadh  Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naeem Mahmood","family":"Asharf","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Biotechnology University of the Punjab  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hira","family":"Abbas","sequence":"additional","affiliation":[{"name":"Reproductive Physiology Laboratory, Department of Animal Sciences Quaid\u2010i\u2010Azam University, Islamabad  Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghazala","family":"Shaheen","sequence":"additional","affiliation":[{"name":"Reproductive Physiology Laboratory, Department of Animal Sciences Quaid\u2010i\u2010Azam University, Islamabad  Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waqar","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Reproductive Physiology Laboratory, Department of Animal Sciences Quaid\u2010i\u2010Azam University, Islamabad  Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayyaba","family":"Afsar","sequence":"additional","affiliation":[{"name":"Department of Community Health Sciences, College of Applied Medical Sciences King Saud University Riyadh  Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Almajwal","sequence":"additional","affiliation":[{"name":"Department of Community Health Sciences, College of Applied Medical Sciences King Saud University Riyadh  Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Shabbir","sequence":"additional","affiliation":[{"name":"Atta\u2010ur\u2010Rahman School of Applied Biosciences (ASAB) National University of Sciences and Technology (NUST)  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huma","family":"Shafique","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine Newcastle University Medical School, Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarwat","family":"Jahan","sequence":"additional","affiliation":[{"name":"Reproductive Physiology Laboratory, Department of Animal Sciences Quaid\u2010i\u2010Azam University, Islamabad  Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,26]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"WhiteleyKS HeggsTG KochH MawerRL ImmelW.Polyolefins.2000.10.1002\/14356007.a21_487[published Online First: Epub Date]."},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01611a109"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00192\u2010016\u20102961\u20104"},{"key":"e_1_2_9_5_1","first-page":"729","article-title":"Experimental tumor induction by plastics from a surgical point of view","volume":"298","author":"Vollmar J","year":"1961","journal-title":"Langenbecks Arch Klin Chir Ver Dtsch Z Chir"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2014.08.048"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2014.03.010"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmt144"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1905840"},{"key":"e_1_2_9_10_1","unstructured":"The mammalian GnRH gene and its pivotal role in reproduction. 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