Human tobacco-related cancers exhibit a high frequency of G to T transversions in the mutation hot spot region of the p53 tumor suppressor gene, possibly the result of specific mutagens in tobacco smoke, most notably benzo [a] An increasing body of molecular epidemiological evidence suggests that regions ofthe p53 gene may be a selective target of environmental carcinogens etiologically associated with specific human cancers (4-19). In this context, a high frequency of G to T transversions in the mutation hot spot regions of the p53 gene (2, 3) have been identified in human hepatocellular carcinomas and strongly correlated with the mutagenic effects of dietary aflatoxin B1 exposurf (4,(13)(14)(15).Similarly, UV-B-specific dipyrimidine G to T transitions in the p53 gene have been characterized in human squamous cell carcinomas of the skin (16,17). Unique mutations in p53 have likewise been reported in radon-associated lung cancers (18) and in human epithelial cells exposed to nickel(II) in vitro (19), providing evidence for an important molecular target for the genotoxic effects of these agents. Of particular clinical and epidemiological interest are the observations of a high frequency of G to T transversions among p53 mutations in tobacco-related human neoplasias, including small-cell and non-small-cell lung cancers (5-8), esophageal carcinomas (10-12), and squamous cell carcinomas of the head and neck (9). In several ofthese studies, the presence of p53 mutations in tumors was strongly correlated with lifetime cigarette consumption (7) or a history of heavy smoking (9).It has been suggested (4-12) that the frequent G to T transversion in the p53 gene in tobacco-related cancers may be associated with specific mutagens in tobacco smoke, most notably activated benzo [a] We have previously investigated the role of p53 alterations in the development and progression of the two-stage mouse skin tumorigenesis model induced by 7,12-dimethylbenz- (24) following hematoxylin/eosin staining. Primary explant cultures of skin tumors were prepared as described (22). Papillomas harvested for analyses were subjected to 35-38 weeks of B[a]P treatment, while carcinomas analyzed were subjected to 50 weeks of carcinogen exposure. In the complete carcinogenesis protocol with DMBA, papillomas and carcinomas used in molecular analyses were obtained from mice subjected to 34-52 weeks of carcinogen exposure. The two-stage carcinogenesis protocol using DMBA as initiator has been described (22

SummaryIn plant development, leaf primordia are formed on the flanks of the shoot apical meristem in a highly predictable pattern. The cells that give rise to a primordium are sequestered from the apical meristem. Maintenance of the meristem requires that these cells be replaced by the addition of new cells. Despite the central role of these activities in development, the mechanism controlling and coordinating them is poorly understood. These processes have been characterized in the Arabidopsis mutant forever young(fey). The fey mutation results in a disruption of leaf positioning and meristem maintenance. The predicted FEY protein shams significant homology to a nodulin and limited homology to various reductases, it is proposed that FEY plays a role in communication in the shoot apex through the modification of a factor regulating meristem development.

A human non-small-cell lung carcinoma cell line, Calu-6 (from an anaplastic carcinoma), was transfected with the Ki-ras-related anti-oncogene Krev-1. Several transfectant lines were obtained that showed a reduced tumorigenicity in nude mice with respect to the parental and control transfected cell lines. This decrease was approximately 50% in tumor incidence at 4 wk after subcutaneous inoculation of the transfected cells. In addition, the volume of the Calu-6 revertant-derived tumors was three to 10 times smaller than that of the equivalent tumors produced by inoculation of the control cell line transfected with the neomycin-resistance gene. Krev-1--transfected cells that exhibited reduced tumorigenicity expressed Krev-1 mRNA and had variable numbers of copies of the Krev-1 gene. Moreover, Krev-1--transfected cells exhibited a more differentiated squamous epithelial morphology than the parental and control cell lines did. Moderately elevated levels of protein kinase C activity were detected in some revertant clones. Such activity correlated with the level of expression of Krev-1 mRNA in most cases. In summary, Krev-1 induced important morphological and biological changes in transfected Calu-6 cells that we interpreted as partial reversion of the malignant phenotype.