Chloral hydrate decreases gap junction communication in rat liver epithelial cells

Abstract

Gap junction communication (GJC) is involved in controlling cell proliferation and differentiation. Alterations in GJC are associated with carcinogenesis, but the mechanisms involved are unknown. Chloral hydrate (CH), a by-product of chlorine disinfection of water, is carcinogenic in mice, and we demonstrated that CH reduced GJC in a rat liver epithelial cell line (Clone 9). To examine the mechanism(s) by which CH inhibits GJC, Clone 9 cells treated with CH were examined using Western blot, real-time polymerase chain reaction, immunocytochemical, and dye-communication techniques. Treatment with CH (0.1–5 mM for 24 h) resulted in a dose-dependent inhibition of GJC as measured by Lucifer yellow dye transfer. Western blot analysis demonstrated expression of connexin (Cx) 43 and 26 in control cells and reduced expression of Cx 43 but not Cx 26 protein from 0.1 to 1 mM CH. CH treatment from 2.5 to 5 mM caused an apparent increase in expression of both connexins that was concomitant with a reduction in mRNA expression for both connexins. Similarly, with immunocytochemistry, a dose-dependent decrease in Cx 43 staining at sites of cell–cell contact was apparent in CH (0.5–5 mM)-treated cultures, whereas no Cx 26 staining was observed. Thus, Clone 9 cells contain two types of connexins but only one type of plasma membrane channel. Understanding of the regulation of connexin may shed light on mechanisms responsible for inhibition of GJC by chemical carcinogens.

Efficacy and safety of chloral hydrate in auditory brainstem response test: A systematic review and single‐arm meta‐analysis

“…43 Studies in mice show that high-dose chloral hydrate occasionally induces liver disease, adenomas or tumours. 44 However, there is currently no conclusive evidence to support the causal relationship between exposure to chloral hydrate and cancer development in humans, and the effects of chloral hydrate in humans are unknown. 45 In this study, the authors reviewed chloral hydrate usage in ABR tests by systematically searching large medical databases, the largest databases to date with the largest sample size.…”

“…Another concern is the potential carcinogenicity of chloral hydrate because chloral hydrate is a major metabolite of trichloroethylene, which is capable of inducing malignancy in rodents and has been listed by the International Agency for Research on Cancer (IARC) of the World Health Organization (WHO) as a probable human carcinogen (Group 2A) 43 . Studies in mice show that high‐dose chloral hydrate occasionally induces liver disease, adenomas or tumours 44 . However, there is currently no conclusive evidence to support the causal relationship between exposure to chloral hydrate and cancer development in humans, and the effects of chloral hydrate in humans are unknown 45 …”