High spin states in {sup 154}Dy were populated via the {sup 36}S({sup 122}Sn, 4n) reaction with a 165-MeV beam provided by the 88' cyclotron at LBNL. The target consisted of a stack of three 0.33 mg/cm{sup 2} self-supporting foils. The decay {gamma} rays were detected with Gammasphere spectrometer array, which consisted of 103 Compton-suppressed germanium detectors at the time of the experiment. A total of 1.5 x 10{sup 9} events was collected, with a requirement of {>=} 5 suppressed Ge detectors in prompt coincidence. Previously known bands were extended to higher spins, up to 51hbar, and at least 4 new bands were found, including a pair of strongly coupled high-K bands. Several bands maintain a smooth rotational behavior up to the highest spins observed. Sharp band terminations were observed at high spins with positive and negative parities, in excellent agreement with theoretical calculations based on the configuration-dependent cranked Nilsson-Strutinsky approach.
<div>Abstract<p>We reported recently a marked reduction in IκB kinase α (IKKα) expression in a large proportion of human poorly differentiated squamous cell carcinomas (SCC) and the occurrence of <i>Ikkα</i> mutations in human SCCs. In addition, overexpression of IKKα in the epidermis inhibited the development of skin carcinomas and metastases in mice. However, whether a reduction in IKKα expression promotes skin tumor development is currently unknown. Here, we assessed the susceptibility of <i>Ikkα</i> hemizygotes to chemical carcinogen-induced skin carcinogenesis. <i>Ikkα</i><sup>+/−</sup> mice developed 2 times more papillomas and 11 times more carcinomas than did <i>Ikkα</i><sup>+/+</sup> mice. The tumors were larger in <i>Ikkα</i><sup>+/−</sup> than in <i>Ikkα</i><sup>+/+</sup> mice, but tumor latency was shorter in <i>Ikkα</i><sup>+/−</sup> than in <i>Ikkα</i><sup>+/+</sup> mice. Some of the <i>Ikkα</i><sup>+/−</sup> papillomas and most <i>Ikkα</i><sup>+/−</sup> carcinomas lost the remaining <i>Ikkα</i> wild-type allele. Somatic <i>Ikkα</i> mutations were detected in carcinomas and papillomas. The chemical carcinogen-induced H-<i>Ras</i> mutations were detected in all the tumors. The phorbol ester tumor promoter induced higher mitogenic and angiogenic activities in <i>Ikkα</i><sup>+/−</sup> than in <i>Ikkα</i><sup>+/+</sup> skin. These elevated activities were intrinsic to keratinocytes, suggesting that a reduction in IKKα expression provided a selective growth advantage, which cooperated with H-<i>Ras</i> mutations to promote papilloma formation. Furthermore, excessive extracellular signal-regulated kinase and IKK kinase activities were observed in carcinomas compared with those in papillomas. Thus, the combined mitogenic, angiogenic, and IKK activities might contribute to malignant conversion. Our findings provide evidence that a reduction in IKKα expression promotes the development of papillomas and carcinomas and that the integrity of the <i>Ikkα</i> gene is required for suppressing skin carcinogenesis. [Cancer Res 2007;67(19):9158–68]</p></div>
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Humans are exposed to a wide variety of carcinogenic insults, including endogenous and man-made chemicals, radiation, physical agents, and viruses. The ultimate goal of carcinogenesis research is to elucidate the processes involved in the induction of human cancer so that interventions may be developed to prevent the disease, either in the general population or in susceptible subpopulations. Progress to date in the carcinogenesis field, particularly regarding the mechanisms of chemically induced cancer, has revealed several points along the carcinogenesis pathway that may be amenable to mechanism-based prevention strategies. The purpose of this review is to examine the basic mechanisms and stages of chemical carcinogenesis, with an emphasis on ways in which preventive interventions can modify those processes. Possible ways of interfering with tumor initiation events include the following: i) modifying carcinogen activation by inhibiting enzymes responsible for that activation or by direct scavenging of DNA-reactive electrophiles and free radicals; ii) enhancing carcinogen detoxification processes by altering the activity of the detoxifying enzymes; and iii) modulating certain DNA repair processes. Possible ways of blocking the processes involved in the promotion and progression stages of carcinogenesis include the following: i) scavenging of reactive oxygen species; ii) altering the expression of genes involved in cell signaling, particularly those regulating cell proliferation, apoptosis, and differentiation; and iii) decreasing inflammation. In addition, the utility for mechanism-based cancer prevention research of new animal models that are based on the overexpression or inactivation of specific cancer-related genes is examined.
