Analysis of the c‐myc, K‐ras and p53 Genes in Methylcholanthrene induced Mouse Sarcomas

Abstract

We have examined 63 methylcholanthrene (MCA)-induced mouse sarcomas for possible correlations of mutations involving the c-myc, ras and p53 genes. The c-myc gene was found to be amplified in 18 of these sarcomas (29%). Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and subsequent direct sequencing identified 18 cases carrying K-ras mutation at codons 12, 13 and 61 (29%). No mutation was detected in the H-ras and N-ras genes. Mutations of the p53 gene in exons 5 to 8 were found in 45 cases (71%). Comparison of these mutations revealed that out of 18 cases with c-myc gene amplifications, 10 carried K-ras mutations (56%) and 14 carried p53 mutations (78%). In contrast, among 45 cases of sarcomas without c-myc gene amplification, 8 were found to have K-ras mutations (18%). The same 45 cases were found to have 31 p53 mutations (69%). The present study suggests a strong correlation between c-myc gene amplification and K-ras gene mutation (P< < < <0.01). p53 gene mutation was frequently found among MCA-induced mouse sarcomas, indicating the importance of this mutation in the etiology of these tumors. However, p53 mutations were present in sarcomas regardless of the state of c-myc amplification and K-ras mutation. Therefore, a defect in the p53 gene is independent of amplification of the c-myc gene or point mutation of the K-ras gene.

3-Metilkolantren ve bütil hidroksitoluenle uyarılmış rat akciğer dokularında p-53 ekson 8 geni mutasyon analizi

“…Yapılan in vivo bir araştırmada 3-MC'nin tek bir intraperitoneal dozunun (40mg/kg) 6 saatte Cyp A trensversiyonlu ki-ras mutasyonlarının eşlik etmesi, MC ile oluşan mutasyon spektrumunun, P53 ve ki-ras geni için benzer olduğunu göstermiştir [9]. Aynı araştırmacılar, bu mutasyonların c-myc geni amplifikasyon artışıyla birlikteliğini ispatlamışlardır [25].…”

“…BHT'nin tek doz enjeksiyonunun akciğerde özellikle tip II alveolar epitel hücrelerinde belirgin bir hücre proliferasyonuna neden olduğu, ikinci BHT uygulamasının çok az bir yanıt meydana getireceğini ve üçüncü BHT enjeksiyonundan sonra akciğerde herhangi bir başka hücre hiperplazisi üretmenin mümkün olamayacağını saptamışlardır. Bu da BHT'nin hücresel ve humoral bağışıklık sistemleri üzerinden etkisini gerçekleştirdiğini desteklemektedir [25].…”

Several types of soft tissue sarcomas originate from the malignant transformation of adipose tissue-derived stem cells

“…To disclose the mystery of the malignant transformation of adScs, genetic alterations including abnormalities of the chromosomes and genetic mutations considered to be responsible for the development of different types of tumors were examined (32)(33)(34)(35)(36). We obtained metaphase chromosomes of transformed adScs and found that these cells were aneuploidy, a characteristic of malignant tumors.…”

“…one research group examined Mca-induced mouse sarcomas for mutations in the p53 gene in one experiment. The rate of mutations of the p53 gene in exons 5-8 was 94% (35,36). Here, we examined the state of exons 5-9 for p53, and identified point mutations in the p53 gene.…”

“…alterations of the p53 gene can be acquired somatically or by induction through carcinogens; 74% of these mutations are missense, resulting in full-length, albeit mutant, proteins. This fraction of missense mutations is much higher than in other tumor suppressor genes, and implies that p53 mutant proteins confer some selective advantage in carcinogenesis (33)(34)(35)(36). The vast majority of p53 mutations in human tumors usually occur within four evolutionary conserved domains of the gene located between exons 5 and 8, which contain the sequence-specific dna binding domain of the protein (34).…”