Codon 61 Mutations in the c‐Harvey‐ras Gene in Mouse Skin Tumors Induced by 7,12‐Dimethylbenz[a]anthracene Plus Okadaic Acid Class Tumor Promoters

Abstract

Three okadaic acid class tumor promoters, okadaic acid, dinophysistoxin-1, and calyculin A, have potent tumor-promoting activity in two-stage carcinogenesis experiments on mouse skin. DNA isolated from tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) and each of these tumor promoters revealed the same mutation at the second nucleotide of codon 61 (CAA----CTA) in the c-Ha-ras gene, determined by the polymerase chain reaction procedure and DNA sequencing. Three potent 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters, TPA, teleocidin, and aplysiatoxin, showed the same effects. These results provide strong evidence that this mutation in the c-Ha-ras gene is due to a direct effect of DMBA rather than a selective effect of specific tumor promoters.

Chemical Defenses: From Compounds to Communities

“…OA is known to promote tumors in mice (Fujiki et al, 1989;Sakai and Fujiki, 1991;Fujiki and Suganuma, 1993) and is hypothesized to do so in other animals (Landsberg, 2002). The only study to address the hypothetical role of OA as a natural tumor promoter in wild animals found that Prorocentrum spp.…”

Polygenic Resistance to Mouse Pulmonary Adenomas

“…n PKC is expressed normally in skin and lung, but administration of lung carcinogens markedly downregulates its expression [ 17] . Most tumor promoters affect protein phosphorylation, either by chronically downregulating protein kinase C ( PKC) activity [ 18] or by stimulating phosphoprotein phosphatase [ 19] . Strains of mice sensitive to tumor promotion by butylated hydroxytoluene ( BHT) respond to chronic BHT treatment by a sustained loss of PKC, whereas resistant strains do not [ 20] .…”

In vivo study on the effects of microcystin extracts on the expression profiles of proto-oncogenes (c-fos, c-jun and c-myc) in liver, kidney and testis of male Wistar rats injected i.v. with toxins

“…Recently, MCs were also found to be toxic to the reproductive systems of male mice (Ding et al, 2006). MC-LR or cyanobacterial extracts in drinking water could induce skin tumors in rats and mice after initiation with 7,12-dimethylbenz(a)anthrazene (Fujiki et al, 1989;Falconer, 1991). In addition, glutathione-S-transferase placental form positive foci were detected in liver of rats after intraperitoneal injection of MC-LR and initiation with diethylnitrosamine (Fujiki, 1992;Nishiwaki-Matsushima et al, 1992).…”