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Synergistic effect of MNU and DMBA in mammary carcinogenesis and H-ras activation in female Sprague-Dawley rats.

Abstract：

:The combined application of N-methyl-N-nitrosourea (MNU) and 7,12-dimethylbenz[alpha]anthracene (DMBA) was compared with the administration of each carcinogen alone as to the effectiveness of the induction of mammary carcinomas and the influence of H-ras oncogene activation in female Sprague-Dawley rats. At 50 days of age, group 1 received 30 mg/kg MNU intraperitoneally (i.p.), group 2 received 30 mg/kg DMBA i.p., group 3 received 60 mg/kg MNU i.p., group 4 received 60 mg/ kg DMBA i.p., group 5 received 30 mg/kg MNU followed by 30 mg/kg DMBA i.p., group 6 received 30 mg/kg MNU i.p. and then 30 mg/kg DMBA intravenously (i.v.) and group 7 remained untreated. Animals were killed when the largest mammary tumor reached 1-2 cm in diameter or were necropsied when they were 30 weeks of age. MNU i.p. produced no deaths (groups 1 and 3), however, the i.p. administration of DMBA induced death due to peritonitis (groups 2, 4 and 5), whereas the i.v. administration of DMBA suppressed the death (group 6). All of the tumors produced by MNU were adenocarcinomas of mammary origin. In contrast, DMBA produced tumors of other than mammary origin. The combined treatment with DMBA and MNU increased the mammary carcinogenic effect; it significantly increased the mean number of mammary cancers per rat. With either carcinogen alone and in combination, the mammary carcinomas produced identical adenocarcinoma histology. Of the mammary carcinomas induced by the combined application of MNU and DMBA (group 6), all 11 tumors from five rats showed the GGA to GAA transitional mutation in H-ras codon 12 (38%) and all 18 tumors from the other 10 rats remained as wild-type. An H-ras point mutation at codon 61 was not detected.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Shirai K,Uemura Y,Fukumoto M,Tsukamoto T,Pascual R,Nandi S,Tsubura A

doi

10.1016/s0304-3835(97)00293-0

subject

Has Abstract

pub_date

1997-11-25 00:00:00

pages

87-93

issue

1

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(97)00293-0

journal_volume

120

pub_type

杂志文章

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