ABSTRACT
Objective To investigate the global level of histone 4 lysine 20 monomethylation (H4K20me1) and expression of base excision repair related mRNA in coal-burning-borne endemic arsenism patients and to analyze its relationship with DNA damage,in order to provide a scientific basis in deepening the interpretation of the role of arsenic in inhibiting repair of DNA damage.Methods In 2014,47 hair samples,blood samples and skin tissue samples of the cases in Xingren County Guizhou Province were collected from the voluntary surgical treatment patients with endemic arsenism (15 general pathological change cases,14 precancerous cases and 18 cancerous cases) and 12 controls.The hair arsenic content was tested via the inductively coupled plasma-mass spectrometry method.The expression of histone H4K20me1 in skin tissues was detected via the immunohistochemistry method;quantitative real-time polymerase chain reaction was used to detect the mRNA levels of poly (ADP-ribose) polymerase (PARP1),N-methylation of purine-DNA-glycosylation (MPG) and X-ray repair cross complementary gene 1 (XRCC1);and DNA damage in peripheral blood was detected by single cell gel electrophoresis test,the level of H4K20me1 in peripheral blood cells was detected by using a sandwich enzyme-linked immunosorbent assay.Results Compared with the control group [median (25 ～ 75 percentile):0.15 (0.07-0.23) μg/L],the hair arsenic content in the case group [0.34 (0.17-0.51) μg/L] was significantly increased (Z =6.037,P ＜ 0.05).Compared with the control group (0.32 ± 0.13,0.17 ± 0.12),the modification level of H4K20me1 in peripheral blood with cancerous group (0.62 ± 0.11) was significantly increased,the modification levels of H4K20me1 (0.54 ± 0.20,0.83 ± 0.10) in skin tissues were increased in the precancerous group and cancerous group (P ＜ 0.05).Compared with the control group [0.95 (0.50-1.49),1.12 (0.98-1.48),0.96 (0.67-1.17)],the mRNA expression levels of PARP1 and MPG in cancerous group [0.37 (0.30-0.44),0.38 (0.15-0.48)] were significantly decreased;the mRNA expression levels of XRCC1 [0.48 (0.38-0.89),0.32 (0.20-0.55)] were significantly decreased in the precancerous group and cancerous group (P ＜ 0.05).Compared with the control group (1.19 ± 0.55,1.27 ± 0.51),Tail DNA％ and Tail moment were significantly increased in the general pathological change group (6.49 ± 0.98,6.60 ± 1.11),the precancerous lesion group (11.22 ± 1.40,10.07 ± 1.11),and the cancerous group (20.38 ± 1.72,27.01 ± 1.78,P ＜ 0.05).There was a positive correlation between the degree of skin lesion and modification level of H4K20me1 in peripheral blood and skin tissues and DNA damage levels (TailDNA％,OTM,r =0.885,0.855,0.806,0.883,P ＜ 0.05).There was a positive correlation between modification level of H4K20me1 in peripheral blood and level of DNA damage (TailDNA％,OTM),the level of H4K20me1 protein expression in skin (r =0.535,0.804,0.754,P ＜ 0.05),and a negative correlation with mRNA expression of MPG,XRCC1 and PARP1 (r =-0.563,-0.514,-0.550,P ＜ 0.05).There was a positive correlation between the modification level of H4K20me1 in skin and DNA damage levels (TailDNA％,OTM,r =0.602,0.875,P ＜ 0.05),and a negative correlation with mRNA expression of MPG,XRCC1 and PARP1 (r =-0.492,-0.502,-0.552,P ＜ 0.05).Conclusion The arsenic pollution of coal burning may affect the level of H4K20me1 modification,inhibit mRNA transcriptional expression of PARP1,MPG and XRCC1 genes related with base excision repair,which may lead to increased DNA damage and participate in the occurrence and development of arsenic poisoning skin lesions.
ABSTRACT
Objective Through measuring and analyzing blood Heat shock proteins (HSP) 70 and HSP90 mRNA expression of different levels of arsenic exposure population,to explore the relationship between HSP70 and HSP90 mRNA expression and endemic arsenic poisoning.Methods The study subjects included a total of 226 residents exposed to arsenic via drinking water from two townships in the city of Bayannur (Shengfeng Township and Hangjinhouqishahai Township Wuyuan County) in Inner Mongolia Autonomous Region in 2011.The residents were divided into four groups according to drinking water arsenic concentration:control group (drinking water arsenic concentration ＜ 10 μg/L),low exposure group (drinking water arsenic concentration 10-＜ 100 μg/L),middleexposure group (drinking water arsenic concentration 100-＜ 200 μg/L),and high exposure group (drinking water arsenic concentration ≥200 μg/L).Epidemiological investigation was carried out.Real-time PCR technology was used to detect the expression levels of blood HSP70 and HSP90 mRNA.And the relationships between the expression of HSP70 and HSP90 mRNA and water arsenic and urinary arsenic levels were analyzed.Results ①With the increase of arsenic concentration,the expression level of HSP70 mRNA increased first and then decreased.The HSP70 mRNA in the blood of high exposure group [2.44 × 10-3 (1.72 × 10-3)] and middle exposure group [3.01 × 10-3 (1.95 × 10-3)] were significantly different from that in the control group [2.27 × 10-3 (1.09 × 10-3),P ＜ 0.05].There was significant difference between the middle exposure group [3.01 × 10-3 (1.95 × 10-3)] and the low and high exposure groups [2.38 × 10-3 (1.55 × 10-3),2.44 × 10-3 (1.72 × 10-3),P ＜ 0.05].The expression of HSP70 mRNA in blood of male [2.71 × 10-3 (1.90 × 10-3)] was slightly higher than that of female [2.34 × 10-3 (1.35 × 10-3),t =2.523,P ＜ 0.05].② With the increase of arsenic concentration,the expression level of HSP90 mRNA increased first and then decreased.The expression of HSP90 mRNA in the middle exposure group [1.29 × 10-2(1.04 × 10-2)] was significantly different from that in the control group [1.04 × 10-2 (0.83 × 10-2),P ＜ 0.05].The differences of HSP90 mRNA between the high exposure group [1.19 × 10-2 (0.88 × 10-2)] and the low and middle exposure groups [1.23 × 10-2 (0.68 × 10-2),1.29 × 10-2 (1.04 × 10-2)] were statistically significant (P ＜ 0.05).③The relative expression of HSP70 mRNA showed a U-shaped regression relationship with the level of urinary arsenic exposure (R2 =0.031,P ＜ 0.05),and the expression of HSP90 mRNA was also correlated with urinary arsenic and nail arsenic (R2 =0.049,0.036,P ＜ 0.05).Conclusion Chronic arsenic exposure affects blood HSP70 and HSP90 mRNA expression.
ABSTRACT
Autophagy and oxidative stress, which are closely related, play important roles in cellular stress response, defense function, and damage. Arsenic is one of the chemical pollutant, which is widely distributed in natural environment. International agency for research on cancer (IARC) has made it clear that arsenic and its compounds are carcinogens. However, the mechanism of carcinogenesis induced by arsenic still remains obscure. Recently, researchers have found that autophagy and oxidative stress play an important role in the process of arsenic carcinogenesis. In this paper, we have reviewed the types and regulation of cellular autophagy, the roles of autophagy and oxidative stress in tumorigenesis, and the effects of arsenic on carcinogenesis.