Effect of cisplatin treatment on early activation of oncogenes in vivo.
The aim of the study was to monitor the early effect of cytostatics containing platinum on oncogenes in inbred CBA/Ca mice. In human head-neck tumors after treatment with the Cisplatin supplemented BVM (Bleomycin, Vincristine, Methotrexate) protocol, further surgeries are often necessary due to regional recurrence. Body weight equivalent amounts of human dose of Cisplatin were administered intraperitoneally to 6-8-week-old, inbred, female CBA/Ca mice. Twenty four 48 and 72 hours after the treatment RNA was isolated from the target organs and the quantitative expression of c-myc, Ha-ras and p53 genes was examined by dot-blotting in potential target tissues. Significant overexpression of Ha-ras and p53 genes was measured in the bone marrow. Regarding the expression of Ha-ras gene, a significant increase was also found in the lymph nodes after 48 hours. The p53 expression in the lungs was down-regulated compared to the control group. In the "short-term" in vivo test, 24-hour examination of gene expression and amplification is suitable for detecting the early effects of carcinogenetic exposure. Cisplatin-induced gene expression alterations call attention to its possible role in the development of regional recurrence in patients treated with cisplatin-containing regimens.
Németh
Arpád
A
Departments of Public Health and Preventive Medicine, University of Pécs H-7643 Pecs Szigeti u. 12, Hungary.
Gyöngyi
Zoltán
Z
Nádasi
Edit
E
Ember
Agoston
A
Olasz
Lajos
L
Nyárády
Zoltán
Z
Skapinyecz
Jozsef
J
Ember
István
I
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001853:Bone Marrow / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016259:Genes, myc; D011905:Genes, ras; D015151:Immunoblotting; D007274:Injections, Intraperitoneal; D008168:Lung / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D000970:Antineoplastic Agents; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras); D002945:Cisplatin