The effect of the nucleolar protein ZNF385A on the ribosomal DNA copy number variation in response to Cr(VI)-induced DNA damage

Huadong Xu; Fan Wu; Chan Ding; Yao Qin; Wen Sun; Lingfang Feng; Junfei Chen; Zhaoqiang Jiang; Yongxin Li; Hailing Xia; Jianlin Lou

doi:10.1016/j.ecoenv.2024.117018

The effect of the nucleolar protein ZNF385A on the ribosomal DNA copy number variation in response to Cr(VI)-induced DNA damage

Ecotoxicol Environ Saf. 2024 Sep 10:284:117018. doi: 10.1016/j.ecoenv.2024.117018. Online ahead of print.

Authors

Huadong Xu¹, Fan Wu², Chan Ding¹, Yao Qin¹, Wen Sun¹, Lingfang Feng¹, Junfei Chen¹, Zhaoqiang Jiang¹, Yongxin Li¹, Hailing Xia¹, Jianlin Lou³

Affiliations

¹ School of Public Health, Hangzhou Medical College, Hangzhou, Zhejiang 310013, China.
² Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Interdisciplinary Research Academy (IRA), Zhejiang Shuren University, Hangzhou, Zhejiang 310015, China.
³ School of Public Health, Hangzhou Medical College, Hangzhou, Zhejiang 310013, China; Huzhou Key Laboratory of Precise Prevention and Control of Major Chronic Diseases, School of Medicine, and the First Affiliated Hospital, Huzhou University, Huzhou, Zhejiang 313000, China. Electronic address: jianlinlou@163.com.

PMID: 39260214
DOI: 10.1016/j.ecoenv.2024.117018

Abstract

Hexavalent chromium [Cr(VI)] is a widely distributed carcinogen in industrial contexts and general environmental contexts. Emerging research highlights the central role of ribosomal DNA (rDNA) in DNA Damage Responses (DDRs). However, there remains a lack of investigation into the potential dose-dependent relationship between exposure to Cr(VI) and alterations in rDNA copy number (CN), as well as the related mechanisms underlying these effects. A molecular epidemiological investigation involving 67 workers exposed to Cr(VI) and 75 unexposed controls was conducted. There was a notable increase in ZNF385A expression, variations in rDNA CN, and elevated γH2AX levels in the peripheral blood of Cr(VI)-exposed workers. Restricted cubic spline (RCS) models showed that blood Cr levels in the exposed population exhibited non-linear dose-dependent relationships with γH2AX, rDNA CN, and ZNF385A. Of considerable interest, there were robust and positive associations between ZNF385A and both γH2AX and rDNA CN. Further in vitro experiments provided concrete evidence that Cr(VI) simultaneously caused an increase in ZNF385A expression and variations in rDNA CN. ZNF385A-depleted cells showed increased sensitivity to Cr(VI)-mediated DDRs and alterations in rDNA CN. This study indicated that ZNF385A played a highly significant role in the rDNA CN variation in response to Cr(VI)-induced DNA damage.

Keywords: DNA damage; Hexavalent chromium; Nucleolar protein; Ribosomal DNA; Zinc finger protein 385 A.