Exposure of mice to arsenic and/or benzo[a]pyrene does not increase the frequency of Aprt-deficient cells recovered from explanted skin of Aprt heterozygous mice.
Exposure to inorganic arsenic in drinking water is linked to cancer in humans, but the mechanism of arsenic-induced cancer is not clear. Arsenic is not a powerful point mutagen, but can cause chromosome malsegregation and mitotic recombination, two events that can cause loss of tumor suppressor alleles and thereby contribute to the evolution of cancerous cells. To determine whether arsenic increases the frequency of allele loss due to either malsegregation or mitotic recombination in vivo, Aprt(+/-) hybrid mice were exposed to sodium arsenite (10 mg/L) in their drinking water for 10 weeks. To determine whether arsenic enhances the action of a known mutagen, half of the arsenic-treated mice were exposed to benzo[a]pyrene (BaP) for 8 weeks by skin painting (500 nmoles/week). Cells were taken from painted dorsal skin and cultured in the presence of 2,6-diaminopurine (DAP), to select colonies lacking adenosine phosphoribosyl transferase (Aprt) activity. The frequency of DAP-resistant (DAP(r)) colonies varied substantially within the treatment groups, but there was no significant difference between the groups. Analysis of DNA from DAP(r) colonies suggested that mitotic recombination contributed to the loss of wild-type Aprt allele. Whether arsenic or BaP enhanced or diminished the frequency of this process could not be deduced from these data.
Fischer
Jared M
JM
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Ohio, USA.
Robbins
Susan B
SB
Kannamkumarath
Sasi S
SS
Al-Zoughool
Mustafa
M
Stringer
Saundra L
SL
Talaska
Glenn
G
Caruso
Joseph A
JA
Stambrook
Peter J
PJ
Stringer
James R
JR
D015075:2-Aminopurine / Q000031:analogs & derivatives / Q000494:pharmacology; D000228:Adenine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002478:Cells, Cultured; D005260:Female; D019656:Loss of Heterozygosity / Q000187:drug effects*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009153:Mutagens / Q000633:toxicity; D012867:Skin / Q000187:drug effects / Q000378:metabolism
D009153:Mutagens; D001564:Benzo(a)pyrene; D015075:2-Aminopurine; C007300:2,6-diaminopurine; D000228:Adenine Phosphoribosyltransferase; D001151:Arsenic