Objectives

Differences in cancer incidence between men and women are often explained by differences in environmental exposure, or the influence of sex hormones. However, there is little research on the intrinsic differences in sensitivity to chemical carcinogens.

Methods

To predict and consider related in vivo carcinogenicity tests, changes in gene expression were examined in rats and mice (by gender and organ) due to exposure to carcinogenic chemicals such as phenyl compounds, which among chemicals are the main cause of carcinogenesis.

Results

In the case of male SD rats, the genes IL1B, TNF, NOS2, IL6, and NGF were related, and the probability of carcinogenesis in the urinary bladder, kidney, and oral cavity was high. In female SD rats, the genes ADRB2, TNF, HMOX1, CYP1A1, PTGS2, ILB1, CASP3, POR, PRL, TSC22D1, ATEG, REG1, HRH2, NFE2L2, AKR1C2, ADRB2, NR3C1, IL6, ADRB1, ADRB3, and LPO showed high probability of carcinogenesis in the stomach, liver, and nasal cavity. In the male F344 rat, the genes ACACA, ACSL1, ALB, ALCAM, CYP19A1, PPARA, CYP4A1, ACAA1, and ACOX1 were related, and showed a high probability of carcinogenesis in the liver, kidney, stomach, and urinary bladder. In the female F344 rat, no related genes were found, but a high probability of carcinogenesis was shown in the kidney, ear, Zymbal’s gland, stomach, and liver. In male ICR mice, no related genes and organs with a high probability of carcinogenesis were found, while in female ICR mice, genes for KRAS, ACHE, CAT, CYP3A4, and GPT were involved, and carcinogenesis occurred in the stomach, thyroid gland, ovary, liver, etc. The probability was shown to be high. In BALBc mice, no related genes and organs with a high probability of carcinogenesis were found, while in female BALBc mice, the genes NR1I2, CYP3A4, ABCB1, CYP2B6, PRKDC, CYP2C9, and NCOA1 were related, and the liver, etc., had a high probability of carcinogenesis.

Conclusion

Differences in the epigenetics of each sex begin at the moment of fertilization due to differences in sex chromosome gene expression and metabolic profiles between XX and XY embryos. These fundamental sex differences in nutrient utilization and mitochondrial activity may contribute to sex differences in the metabolic reprogramming of cancer cells, which is important during cancer development, cancer progression, and response to anticancer treatment.

Purpose of review

In this study, I compared and considered the degree of toxicity and genome expression in each male and female gender and organ due to exposure to phenyl compounds (PAH, etc.), which are the basis of benzene toxicity as aromatic hydrocarbons, and conducted future inhalation toxicity tests and related carcinogenicity tests.

Recent findings

Differences in the epigenetics of each sex begin at the moment of fertilization due to differences in sex chromosome gene expression and metabolic profiles between XX and XY embryos. Throughout development, additional processes, such as X-chromosome inactivation and gonadal steroid exposure, further distinguish the sexes.

中文翻译：

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对大鼠和小鼠因接触苯基化合物而按性别划分的致癌性进行系统评价

目标

男性和女性癌症发病率的差异通常可以用环境暴露的差异或性激素的影响来解释。然而，关于化学致癌物敏感性的内在差异的研究很少。

方法

为了预测和考虑相关的体内致癌性测试，研究人员检查了大鼠和小鼠（按性别和器官）由于接触苯基化合物等致癌化学物质而导致的基因表达变化，其中苯基化合物是致癌的主要原因。

结果

雄性SD大鼠中，IL1B、TNF、NOS2、IL6、NGF等基因相关，膀胱、肾、口腔癌变的概率较高。在雌性 SD 大鼠中，基因 ADRB2、TNF、HMOX1、CYP1A1、PTGS2、ILB1、CASP3、POR、PRL、TSC22D1、ATEG、REG1、HRH2、NFE2L2、AKR1C2、ADRB2、NR3C1、IL6、ADRB1、ADRB3 和 LPO 显示胃、肝、鼻腔癌变的可能性较高。在雄性F344大鼠中，基因ACACA、ACSL1、ALB、ALCAM、CYP19A1、PPARA、CYP4A1、ACAA1和ACOX1相关，并且在肝、肾、胃和膀胱中表现出高概率的致癌作用。在雌性F344大鼠中，没有发现相关基因，但在肾脏、耳朵、Zymbal腺、胃和肝脏中显示出很高的致癌可能性。在雄性ICR小鼠中，未发现相关基因和高概率致癌的器官，而在雌性ICR小鼠中，涉及KRAS、ACHE、CAT、CYP3A4和GPT基因，致癌发生在胃、甲状腺、卵巢、肝脏等。显示概率很高。在BALBc小鼠中，未发现相关基因和高概率致癌的器官，而在雌性BALBc小鼠中，相关基因NR1I2、CYP3A4、ABCB1、CYP2B6、PRKDC、CYP2C9、NCOA1、肝脏等，致癌的可能性很大。

结论

由于 XX 和 XY 胚胎之间性染色体基因表达和代谢谱的差异，每个性别的表观遗传学差异从受精那一刻开始。这些营养利用和线粒体活性方面的基本性别差异可能导致癌细胞代谢重编程的性别差异，这在癌症发生、癌症进展和抗癌治疗反应中非常重要。

审查目的

在这项研究中，我比较并考虑了由于接触苯化合物（PAH等）而导致的每个男性和女性性别和器官的毒性程度和基因组表达，苯基化合物是苯作为芳香烃的毒性基础，并进行了未来的研究。吸入毒性试验及相关致癌性试验。

最近的发现

由于 XX 和 XY 胚胎之间性染色体基因表达和代谢谱的差异，每个性别的表观遗传学差异从受精那一刻开始。在整个发育过程中，X染色体失活和性腺类固醇暴露等其他过程进一步区分了性别。