Table 1.

Functional genomics and omics approaches to study benzene and formaldehyde toxicity

Organism		Functional genomic/omic screens	Cell type	Genes covered	Advantages	Limitations	Tested
in vitro	Yeast	Parallel Deletion Analysis (PDA)38–42	Saccharomyes cervisiae	All non-essential genes	Yeast genome well annotated, a good model for human/higher eukaryote disease. Quantitative, high- throughput.	Not all yeast genes have human homologs	BZ (HQ, BT, CAT)8 FA50,52
	Chicken	DT-40 cells—avian leukosis virus transformed32,33	B lymphocytes	DNA repair–pathway genes	Highly effective gene targeting, rapid gowth rate	Few pathways covered	FA29,35
	Mouse	Mouse haploid embryonic stem cells (ESC)56,57–61	ESC	All non-lethal genes	Mouse more relevant to human	Not high-throughput	BZ, FA not tested
	Human	Human haploid cell line (KBM 7)31	CML bone marrow cells	All genes except those on chromosome 8	Genes whose insertional disruption allows cells to survive/proliferate can be identified	Chromosome 8 genes not disrupted	FA, HQ55
in vivo	Human	Chromosome-wide association study (CWAS)68	Human lymphocytes, circulating HSC/HPC	All human chromosomes	Detects aneuploidy in all 24 chromosomes on a single 8-square slide		BZ,16,17
		Transcriptomics
		-Gene expression microarrays	Human PMBC	Illumina HumanRef-8 V2 BeadChip targets	Study design with replicates can minimize potential confounding and experimental variability.	Limited by probes on chips	BZ13, 14,73
		-RNA sequencing	Human PMBC	All poly-A-enriched transcripts	Wider dynamic range than microarrays. Can detect coding and non-coding transcripts and splice variants	Expensive. Variability arises in experimental steps.	BZ15

BT, 1,2,4-benzenetriol; BZ, benzene; CML, chronic myeloid leukemia; CWAS, chromosome-wide association study; ESC, embryonic stem cell; FA, formaldehyde; HPC, hematopoietic progenitor cell; HQ, hydroquinone; HSC, hematopoietic stem cell; PBMC, peripheral blood mononuclear cells; PDA, parallel deletion analysis.