Combined in utero and juvenile exposure of mice to arsenate and atrazine in drinking water modulates gene expression and clonogenicity of myeloid progenitors.
The effects of arsenate (As) and atrazine (Atr) on myeloid progenitors (colony-forming unit-granulocyte/macrophage, CFU-GM) cells derived from bone marrow were studied in male and female mice after combined in utero and juvenile exposure. Female adult mice were treated with arsenate in drinking water during gestation. Then, separate groups of males and females' offspring were exposed for 4 months to atrazine, to additional arsenate or to co-exposure of atrazine and arsenate together in drinking water. In male mice, arsenate and the combined exposure did not modulate the percentage of CFU-GM progenitors, whereas atrazine significantly decreases the clonogenicity of myeloid cells. In females, the percentage of CFU-GM significantly decreased after atrazine exposure did not change with arsenate treatment, but dramatically increased after the combined exposure. The expression of estrogen receptors alpha (ERalpha) and beta (ERbeta) in bone marrow cells was investigated, and an up-regulation of receptor beta was observed in both genders. A gene expression profile was generated using nylon membranes spotted with 1185 cancer-related genes. Results from microarrays indicate that atrazine alone did not stimulate the expression of any of the genes analysed in both male and female. Arsenic induced gene expression modulation only in female. Major significant changes on the gene expression resulted following the co-exposure to arsenic and atrazine in both male and female.
Cimino-Reale
Graziella
G
Joint Research Centre, Physical and Chemical Exposure Unit (PCE), Institute for the Health and Consumer Protection, via E. Fermi 1, 21020 Ispra (VA), Italy. graziella.cimino@jrc.it
Ferrario
Daniele
D
Casati
Barbara
B
Brustio
Roberta
R
Diodovich
Cristina
C
Collotta
Angelo
A
Vahter
Marie
M
Gribaldo
Laura
L
D000284:Administration, Oral; D000818:Animals; D001149:Arsenates / Q000633:toxicity*; D001280:Atrazine / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002999:Clone Cells / Q000187:drug effects; D004326:Drinking; D004338:Drug Combinations; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006540:Herbicides / Q000633:toxicity*; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008815:Mice, Inbred Strains; D023461:Myeloid Progenitor Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D013723:Teratogens / Q000633:toxicity*; D000097983:ERRalpha Estrogen-Related Receptor
D001149:Arsenates; D001280:Atrazine; D004338:Drug Combinations; D006540:Herbicides; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013723:Teratogens; D000097983:ERRalpha Estrogen-Related Receptor; C098925:Esrrb protein, mouse; C025657:arsenic acid