Whole DNA methylome profiling in mice exposed to secondhand smoke.
Aberration of DNA methylation is a prime epigenetic mechanism of carcinogenesis. Aberrant DNA methylation occurs frequently in lung cancer, with exposure to secondhand smoke (SHS) being an established risk factor. The causal role of SHS in the genesis of lung cancer, however, remains elusive. To investigate whether SHS can cause aberrant DNA methylation in vivo, we have constructed the whole DNA methylome in mice exposed to SHS for a duration of 4 mo, both after the termination of exposure and at ensuing intervals post-exposure (up to 10 mo). Our genome-wide and gene-specific profiling of DNA methylation in the lung of SHS-exposed mice revealed that all groups of SHS-exposed mice and controls share a similar pattern of DNA methylation. Furthermore, the methylation status of major repetitive DNA elements, including long-interspersed nuclear elements (LINE L1), intracisternal A particle long-terminal repeat retrotransposons (IAP-LTR), and short-interspersed nuclear elements (SINE B1), in the lung of all groups of SHS-exposed mice and controls remains comparable. The absence of locus-specific gain of DNA methylation and global loss of DNA methylation in the lung of SHS-exposed mice within a timeframe that precedes neoplastic-lesion formation underscore the challenges of lung cancer biomarker development. Identifying the initiating events that cause aberrant DNA methylation in lung carcinogenesis may help improve future strategies for prevention, early detection and treatment of this highly lethal disease.
Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
Stella
S
Tommasi
Albert
A
Zheng
Jae-In
JI
Yoon
Arthur Xuejun
AX
Li
Xiwei
X
Wu
Ahmad
A
Besaratinia
D000818:Animals; D019175:DNA Methylation / Q000187:drug effects*; D016678:Genome / Q000187:drug effects; D020084:Long Interspersed Nucleotide Elements / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020086:Short Interspersed Nucleotide Elements / Q000187:drug effects; D012907:Smoking / Q000235:genetics; D014028:Tobacco Smoke Pollution
D014028:Tobacco Smoke Pollution