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Gender-dependent effects of gonadectomy on lung carcinogenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female and male A/J mice Ninomiya, Fumiko 二宮, 芙美子 ニノミヤ, フミコ open access Copyright: © Ninomiya et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0]. lung tumorigenesis gonadectomy sex hormone 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone A/J mouse The present study was conducted to investigate the effects of gonadectomy on lung carcinogenesis in female and male mice, and to determine an association between sex hormone and lung carcinogenesis. Female and male A/J mice were divided into gonadectomized and unoperated control groups and all animals were treated intraperitoneally with 1 or 2 injections of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) at the dose of 2 mg/mouse. The mice were sacrificed 18 or 56 weeks after surgery. Serum levels of estradiol in females and testosterone in males were confirmed to be decreased by gonadectomy. Lung white nodules were detected in all mice of all groups. In the control groups of 18- and 56-week studies, the multiplicities of lung nodules in females were significantly greater than in males. In males in the 56-week study, the multiplicity of macroscopical lung nodules, bronchiolo-alveolar hyperplasias, adenomas and tumors (adenomas and adenocarcinomas) showed significant increase with castration. In females in the 18-week study, the multiplicity of adenomas decreased significantly by ovariectomy. Based on the results of the present study, female A/J mice were confirmed to be more susceptible to NNK-induced lung carcinogenesis than males. Furthermore, it was suggested that the process is inhibited by testosterone and accelerated by estradiol. These findings indicate the possibility that sex hormones play important roles in determining sex differences in lung carcinogenesis in the A/J mice initiated by NNK. eng doctoral thesis P https://kagawa-u.repo.nii.ac.jp/records/199 https://doi.org/10.3892/or.2013.2759 https://dl.ndl.go.jp/pid/11344365 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839949/ 24085151 500001358757 甲第584号 博士（医学） 2014-03-24 16201 香川大学 Kagawa University https://kagawa-u.repo.nii.ac.jp/record/199/files/Med_A584.pdf application/pdf 2.9 MB 2020-10-22 https://kagawa-u.repo.nii.ac.jp/record/199/files/Med_A584_abstract.pdf application/pdf 346.7 kB 2020-10-22 https://kagawa-u.repo.nii.ac.jp/record/199/files/Med_A584_result.pdf application/pdf 328.5 kB 2020-10-22