326 Abstracts/Lung Cancer 13 (1995) 323-356

incidence rates are most likely related to the pattern of past smoking habits: the percentage of male adult smokers in the southern part of the Netherlands decreased from 95% in 1960 to 40% in 1981 and the percentage of female adult smokers increased from 27% in 1960 to 40% in 1967, slightly decreasing only after 1979. In view of the trends in smoking behaviour, the incidence rates for male lung cancer will decline further, whereas female lung cancer incidence may decrease after the year 2000.

Increasing lung cancer mortality rates in the elderly: A manifestation of differential survival Riggs JE. Department of Neurology, West Mrginia Universiiy, School

of Medicrne, t?O. Box 9180, Morgantown, WV 26506-9180. Regul Toxic01 Pharmacol 1995;2 1:370-4.

Lung cancer mortality rates in the elderly are increasing. Using published United States mortality data, annual age-specific lung cancer mortality rates from 1968 to 1989 were determined for age groups over age 50 and compared to corresponding annual age group population sizes. Rising lung cancer mortality rates among the elderly in the United States from 1968 to 1989 were increasingly dependent, with increasing age, upon increasing age group population size. This finding suggests that differential survival, and its effect upon the surviving gene pool in an aging population, may account for observed increasing lung cancer mortality rates in recent successive elderly cohorts. That is, increasing lung cancer mortality rates in the elderly may reflect changes in the genetic susceptibility of the surviving population rather than changes in environmental exposures.

Basic biology

Insulin-like growth factor-I is an autocrine regulator for the brain metastatic variant of a human non-small cell lung cell line Hwang C-C, Fang K, Li L, Shih SH. Department ofBio/o~, National

Taiwan Normal University, Taipei II 718. Cancer Lett 1995;94: 157-63. Insulin-like growth factor (IGF-I) is associated with autocrine and

paracrine stimulation for cell growth and development of brain tumor cells. The function of IGF-I in the brain metastatic variant of human lung cancer cells is investigated. The cells used here were derived in vivo with intracarotid injection of human non-small cell lung carcinoma NCIH226. The tumor was developed as a cultured cell line, H226Br. Unlike the parental cells, H226Br was tumorigenic in nu/nu nude mice. Reverse transcriptase-polymerase chain reaction showed that IGF-I transcript of H226Br is increased compared to that of parental cells. The amount of IGF-I secreted in cultured medium of H226Br is higher than that of cultured parental cells. The IGF-I receptor-specific antibody, 6IR3, inhibits H226Br growth in serum-free culture. The results established that IGF-I is an autocrine growth regulator for human non- small cell lung cancer cells that progressed to brain.

Loss of heterozygosity at 9~23 defines a novel locus in non- small cell lung cancer Neville EM, Stewart M, Myskow M, Donnelly RJ, Field JK. Molecular Genetics Oncology Group, Department Clinical Dental Sciences, The University of Liverpool, PO Box 147, Liverpool L69 3BX. Oncogene 1995;11:581-5.

Genetic studies have previously demonstrated cytogenetic deletions and allelic imbalance or loss of heterozygosity (LOH) on the p arm of chromosome 9, in a number of tumour types. We have analyscd 45

Non-Small Cell Lung Cancers (NSCLC) with a panel of highly polymorphic microsatellite markers on chromosome 9. Our results indicate that loss on 9p is concentrated within the D9S156-D9S161 region with 44% (20/45) LOH, however the area with minimal loss in this set of lung tumours was found at D9S157 (9p23), with 30% LOH (10/33), whereas loss at the IFNA locus was only found in 6% (2/34) tumours. Five of the lung tumours in this study which demonstrated LOH at D9S157 retained heteroqgosity at the adjacent informative markers lying centromeric and telomeric to D9S157. No correlations were found between any ofthe clinico-pathological parameters and LOH on 9p or at the D9Sl57 locus. The results of this study indicates the presence of a further putative tumour suppressor gene on 9p at the D9Sl57 locus (9~23) to be most likely involved in the pathogenesis of non-small cell lung cancer,

Retinoic acid modulates epidermal growth factor receptor expression in human lung epithelial cancer cells Fang K, Mukhopadhyay T, Shih SH. Department o/Wology, National

Tarwan Normal Universily. Taipei. J Biomed Sci 1995;2:256-62. In human lung epithelial cancer cell line H460, an accumulation of

epidermal growth factor receptors (EGF-R) was observed following treatment with 1 iM retinoic acid. An increase in lZ’I-labeled EGF binding capacity was detected, which reached its highest level after 48 h of incubation with retinoic acid. Transiently increased autophosphorylation of EGF-R after 48 h of retinoic acid treatment correlated with enhancement of EGF binding capacity on the H460 cell surface. Nuclear run-on analysis indicated that retinoic acid upregulates transcription of the EGF-R gene, reaching a maximum at 48 h and decreasing after 72 h of treatment. When retinoic acid-treated cells were chased in drug-free medium, the increased EGF-R transcript level remained unchanged. Up-regulated expression of EGF-R in H460 cells is reflected by their increasing tumorigenicity phenotype The results demonstrate that retinoic acid induces EGF-R synthesis in human lung cancer cells.

No occurrence of DNA polymerase R gene mutation in human lung carcinoma cell lines with K-ras, ~53, or Rb gene alterations Fujishita T, Mizushima Y, Kashii T, Kawasaki A, Kobayashi M. fst Department ofInternal Medicine, Medical/Pharmaceutical bikersi@!

2630 Sugitani, Toyama 930-01. Oncol Rep 1995;2:755-7. In order to investigate the relationship between a potential defect in

the DNA repair system and human lung carcinogenesis, we examined the entire coding region of the human DNA polymerase 8 gene using the reverse transcription-polymerase. chain reaction (RT-PCR)/single- strand conformation polymorphism (SSCP) method in 3 1 human lung carcinoma cell lines (I8 non-small cell lung carcinoma (NSCLC) cell lines and 13 small cell lung carcinoma (SCLC) cell lines, 4 cell lines with K-ras point mutation, 9 with ~53 point mutation, 3 with retinoblastoma susceptibility (Rb) gene alteration). Mutation of the polymerase IJ gene was undetectable in all ofthem. These results suggest that mutations of the DNA polymerase R gene is extremely rare if it occurs at all in human lung cancer, and may have no relation with K- ras, ~53, or Rb gene alterations.