Apc-Mutant Kyoto Apc Delta (KAD) Rats Are Susceptible to 4-NQO-Induced Tongue Carcinogenesis

Despite widening interest in the possible association between infection/ inflammation and cancer development, knowledge of this issue in relation to oral cancer remains inadequate. This study aimed to determine the susceptibility of Apc-mutant Kyoto Apc Delta (KAD) rats, which are vulnerable to deve...

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Main Authors: Takuji Tanaka, Masahito Shimizu, Takahiro Kochi, Yohei Shirakami, Takayuki Mori, Naoki Watanabe, Takafumi Naiki, Hisataka Moriwaki, Kazuto Yoshimi, Tadao Serikawa, Takashi Kuramoto
Format: Article
Language:English
Published: MDPI AG 2014-07-01
Series:Cancers
Subjects:
Online Access:http://www.mdpi.com/2072-6694/6/3/1522
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author Takuji Tanaka
Masahito Shimizu
Takahiro Kochi
Yohei Shirakami
Takayuki Mori
Naoki Watanabe
Takafumi Naiki
Hisataka Moriwaki
Kazuto Yoshimi
Tadao Serikawa
Takashi Kuramoto
author_facet Takuji Tanaka
Masahito Shimizu
Takahiro Kochi
Yohei Shirakami
Takayuki Mori
Naoki Watanabe
Takafumi Naiki
Hisataka Moriwaki
Kazuto Yoshimi
Tadao Serikawa
Takashi Kuramoto
author_sort Takuji Tanaka
collection DOAJ
description Despite widening interest in the possible association between infection/ inflammation and cancer development, knowledge of this issue in relation to oral cancer remains inadequate. This study aimed to determine the susceptibility of Apc-mutant Kyoto Apc Delta (KAD) rats, which are vulnerable to developing inflammation-associated colorectal carcinogenesis, to 4-nitroquinoline 1-oxide (4-NQO)-induced tongue carcinogenesis in order to clarify the role of inflammation in oral cancer. KAD (20 males and 22 females) and F344/NS1c (22 males and 23 females) rats received drinking water with or without 4-NQO (20 ppm) for eight weeks. Histopathological and immunohistochemical analyses of the tongue were performed at week 20. Additionally, the mRNA expression of inflammatory cytokines in the tongue mucosa was determined at week 8. Tongue squamous cell carcinoma (SCC) developed in the KAD and F344/NS1c rats that received 4-NQO. Regardless of gender, the incidence and multiplicity of tongue SCC were greater in the KAD rats than in the F344/NS1c rats. In addition, the multiplicity of tongue SCC in the female KAD rats was significantly greater than that observed in the male KAD (p < 0.01) and female F344/NS1c rats (p < 0.05). The levels of inflammation and the mRNA expression of inflammatory cytokines in the tongue in the 4-NQO-treated female KAD rats were the highest among the rats given 4-NQO. These results show that KAD rats, particularly females, are susceptible to 4-NQO-induced tongue carcinogenesis, suggesting the utility of models employing KAD rats for investigating the pathobiology of oral (tongue) carcinogenesis associated with inflammation.
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spelling doaj.art-8831aa9ea66e49c8a1e88462bf5fc9cc2023-09-03T09:48:14ZengMDPI AGCancers2072-66942014-07-01631522153910.3390/cancers6031522cancers6031522Apc-Mutant Kyoto Apc Delta (KAD) Rats Are Susceptible to 4-NQO-Induced Tongue CarcinogenesisTakuji Tanaka0Masahito Shimizu1Takahiro Kochi2Yohei Shirakami3Takayuki Mori4Naoki Watanabe5Takafumi Naiki6Hisataka Moriwaki7Kazuto Yoshimi8Tadao Serikawa9Takashi Kuramoto10Department of Diagnostic Pathology (DDP) & Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, 7-1 Kashima-Cho, Gifu 500-8513, JapanDepartment of Internal Medicine/Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, JapanDepartment of Internal Medicine/Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, JapanDepartment of Internal Medicine/Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, JapanDepartment of Pharmacy, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki 503-8502, JapanDepartment of Diagnostic Pathology (DDP) & Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, 7-1 Kashima-Cho, Gifu 500-8513, JapanDepartment of Clinical Laboratory, Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu 500-8513, JapanDepartment of Internal Medicine/Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, JapanThe Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, JapanThe Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, JapanThe Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, JapanDespite widening interest in the possible association between infection/ inflammation and cancer development, knowledge of this issue in relation to oral cancer remains inadequate. This study aimed to determine the susceptibility of Apc-mutant Kyoto Apc Delta (KAD) rats, which are vulnerable to developing inflammation-associated colorectal carcinogenesis, to 4-nitroquinoline 1-oxide (4-NQO)-induced tongue carcinogenesis in order to clarify the role of inflammation in oral cancer. KAD (20 males and 22 females) and F344/NS1c (22 males and 23 females) rats received drinking water with or without 4-NQO (20 ppm) for eight weeks. Histopathological and immunohistochemical analyses of the tongue were performed at week 20. Additionally, the mRNA expression of inflammatory cytokines in the tongue mucosa was determined at week 8. Tongue squamous cell carcinoma (SCC) developed in the KAD and F344/NS1c rats that received 4-NQO. Regardless of gender, the incidence and multiplicity of tongue SCC were greater in the KAD rats than in the F344/NS1c rats. In addition, the multiplicity of tongue SCC in the female KAD rats was significantly greater than that observed in the male KAD (p < 0.01) and female F344/NS1c rats (p < 0.05). The levels of inflammation and the mRNA expression of inflammatory cytokines in the tongue in the 4-NQO-treated female KAD rats were the highest among the rats given 4-NQO. These results show that KAD rats, particularly females, are susceptible to 4-NQO-induced tongue carcinogenesis, suggesting the utility of models employing KAD rats for investigating the pathobiology of oral (tongue) carcinogenesis associated with inflammation.http://www.mdpi.com/2072-6694/6/3/1522tonguecarcinogenesissusceptibilityinflammationApc mutant rats
spellingShingle Takuji Tanaka
Masahito Shimizu
Takahiro Kochi
Yohei Shirakami
Takayuki Mori
Naoki Watanabe
Takafumi Naiki
Hisataka Moriwaki
Kazuto Yoshimi
Tadao Serikawa
Takashi Kuramoto
Apc-Mutant Kyoto Apc Delta (KAD) Rats Are Susceptible to 4-NQO-Induced Tongue Carcinogenesis
Cancers
tongue
carcinogenesis
susceptibility
inflammation
Apc mutant rats
title Apc-Mutant Kyoto Apc Delta (KAD) Rats Are Susceptible to 4-NQO-Induced Tongue Carcinogenesis
title_full Apc-Mutant Kyoto Apc Delta (KAD) Rats Are Susceptible to 4-NQO-Induced Tongue Carcinogenesis
title_fullStr Apc-Mutant Kyoto Apc Delta (KAD) Rats Are Susceptible to 4-NQO-Induced Tongue Carcinogenesis
title_full_unstemmed Apc-Mutant Kyoto Apc Delta (KAD) Rats Are Susceptible to 4-NQO-Induced Tongue Carcinogenesis
title_short Apc-Mutant Kyoto Apc Delta (KAD) Rats Are Susceptible to 4-NQO-Induced Tongue Carcinogenesis
title_sort apc mutant kyoto apc delta kad rats are susceptible to 4 nqo induced tongue carcinogenesis
topic tongue
carcinogenesis
susceptibility
inflammation
Apc mutant rats
url http://www.mdpi.com/2072-6694/6/3/1522
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