Preferential induction of guanine deletion at 5 '-GGGA-3 ' in rat mammary glands by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

Citation
E. Okochi et al., Preferential induction of guanine deletion at 5 '-GGGA-3 ' in rat mammary glands by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, CARCINOGENE, 20(10), 1999, pp. 1933-1938
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CARCINOGENESIS
ISSN journal
0143-3334 → ACNP
Volume
20
Issue
10
Year of publication
1999
Pages
1933 - 1938
Database
ISI
SICI code
0143-3334(199910)20:10<1933:PIOGDA>2.0.ZU;2-S
Abstract
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is known to induce a characteristic mutation, G deletion at the 5'-GGGA-3' site, preferentially in the lad transgene of the colonic mucosa of Big Blue(R) rats (BBR) and m ice and specifically in the Ape gene of rat colon tumors. In this study, la d mutations of the mammary glands in PhIP-treated rats were investigated. S ix-week-old female (BBR x Sprague-Dawley)F-1 rats were administered 10 gava ges of 65 mg/kg/day PhIP, Mammary ducts were collected from the macroscopic ally normal mammary tissue of PhIP-treated and untreated rats at 56-69 week s of age by collagenase treatment. The mutant frequencies were 25 +/- 2.1x1 0(-6) in control rats and 323 +/- 44 x 10(-6) in the PhIP-treated rats. By sequencing 40 and 177 mutants in the control and PhIP-treated groups, respe ctively, 34 and 149 mutations were considered independent mutations. In the control group, G:C-->A:T transitions at CpG sites dominated and no G:C del etions were detected. In the PhIP-treated group, G:C-->T:A transversions we re most frequent (43%), followed by single base pair deletions of G:C (21%) . A total of nine deletions were at 5'-GGGA-3' sites, accounting for 29% of the G:C deletions and 6% of the 149 total mutations. Clusters of more than three mutations at one nucleotide position were observed at 12 positions a nd two were G deletions at 5'-GGGA-3' sites. Comparison of the PhIP-induced mutations in the mammary glands with those previously reported in the colo n revealed that G:C-->T:A transversions occurred at a significantly higher frequency in the mammary glands and that G:C deletions occurred at a signif icantly lower frequency. However, the signature mutation, G deletion at the 5'-GGGA-3' site, was commonly observed in both tissues.