192 Abstracts/Lung Cancer 13 (1995) JM-232

CYP2D6, CYPZEI, ad CYPIAI, as well as for glutathione S-trans- ferase Ml (GSTMI). Statistical differences among adduct levels for the study variables, including genotypes, were assessed by the two-sided Student’s t test or the Mann-Whitney U test. Results: Higher 7-methyl- dGMP adduct levels were associated with CYP2D6 genotypes (p = .Ol), consistent with the repolts of the increased risk of lung cancer associated with this genotype. Higher adduct levels were also associated with CYP2El minor alleles (P = .05). In both cases, the association was attributed mostly to individuals with low serum cotinine levels (p = .004 and P = .05, respectively), suggesting that the effect of the genotypes is mostly in nonsmokers exposed to either passive tobacco smoke or to N-nitrosamine exposures other than tobacco smoke. Separately, the presence of PAH-dGMP adducts was associated with the GSTMl null

genotype (absence ofthe gene) (odds ratio = 8.6; 95% confidence interval = 1.03-00). Concfusions: This study tinds that the levels of two different carcinogen-DNA adducts vary in lung tissue (an important target tissue) in association with three separate genetic polymorphisms (i.e., CYP2D6, CYP2El.andGSTMl). CYP2D6andCYF2EI genotypesarcassociated with higher 7-methyldGMP levels, while the GSTMl null genotype is associated with higher numbers of PAHdGMP adducts. These findings suggest that genetic polymorphisms are predictive of Carcinogen-DNA adduct levels and would thus be predictive of an individual’s lifetime response to carcinogen exposure.

Telomerase activity in small-cell and non-small-cell lung cancers Hiyama K, Hiyama E, Ishioka S, Yamakido M, Inai K, Gazdar AF et al. Dept. of Cell Biology/?Veuroscience, Texas University SW Medical Cenrea 5323 Harry Hines Blvd., DaNas, TX 75235-9039. J Natl Cancer Inst 1995;87:895- 902.

Background: Telomerase is an enzyme that adds hexameric lTAGGG nucleotide repeats onto the ends of vertebrate chromosomal DNAs (i.e., telomeres) to compensate for losses that occur with each round of DNA replication. Somatic cells do not have telomerase activity and stop dividing when the telomeric ends of at least some chromosomes have been shonened to a critical length. It has been suggested that immortalized cells (including some, but probably not all, cancer cells) continue to proliferate indefinitely because they express telomerase. Purpose: To investigate whether expression of telomerase is a prerequisite for the development of naturally occurring human cancers. we assayed the levels of telomerasc activity in specimens of human lung tumor and adjacent normal tissue. Methods: Using a polymerase chain reaction-based assay, we examined telomerase activity in 136 primary lung cancer tissues and 68 adjacent noncancerous tissues obtained by surgical resection. We also studied telomerasc activity in four primary and 23 metastatic lesions obtained through biopsy (two patients) or autopsy (IO patients). Relative telomerasc activity levels were estimated by serial dilutions of extracts prepared from the specimens. Telomerase activity was also assayed in extracts of cells present in pleural fluids from three patients with adenccarcinoma of the lung. Results: Among surgically resected samples, telomerase activity was detected in I09 (80.1%) of 136 primary lung cancer tissues and in three (4.4%) of 68 normal adjacent tissues. All 11 surgically resected specimens ofprimary small-cell lung cancer (from 11 patients) revealed high levels of telomerase activity, whereas the activity ranged from undetectable to high levels in the 125 surgically resected specimens of primary non-smallqell lung cancer tissue (from 125 patients). Generally, high levels of telomerase activity were observed in metastatic lesions and tumors with altered telomere length. A few primary and, surprisingly, some metastatic tumors did not appear to have detectable telomerase activity. Telomerasc activity was, however, detected in cells present in all tested pleural fluids obtained (from three patients with adenocarcinoma ofthe lung). Conclusion: The subset of non-small-cell

lung cancers that exhibits only low or undetectable levels of telomerase activity may contain primarily mortal cancer cells. Cancers that exhibit high levels of telomerase activity, such as all of the small- cell lung cancers examined in this study, are likely to consist mainly of immortal cells. Implications: Telomerase activity may be useful both as a diagnostic marker to detect the existence of immortal lung cancer cells in clinical materials and as a target for therapeutic intervention.

Studies on the autologous tumor killing activity and lymphocyte subset in patients with lung cancer Arano Y. Department o/Surgery, School of Medicine, Kanazawa University, 13-J Takaramachi. Kanazawa 920. Biotherapy (Japan) 1995;9:709-10.

Autologous tumor killing (An<) activity and proportional change in the subsets in the peripheral blood lymphocytes (PBL) and regional lymph node lymphocytes (RLNL) were analyzed in patients with lung cancer. The ATK activities of PBL decreased with the progression of the disease and nodal metastasis, whereas those of RLNL decreased with the progression of nodal metastasis. The RLNL subsets demonstrated a decrease in the number of the CD4’ LeuS- cells. CDS’ CDIl- cells, and CD3’ HLA-DR+ cells, and an increase in the number of the CD4’ Leul’ cells with progression of nodal metastasis. These results suggest that the systemic immune activity has no correlation with regional immune activity.

CYPlAl and CYP2El polymorphism and lung cancer, case- control study in Rio de Janeiro, Brazil Sugimura H, Hamada GS, Suzuki I, Iwase T, Kiyokawa E, Kino I et al. 1st Department of Pathology Hamamatsu Univ. School of Medicine, 3600 Handa-cho, Hamamatsu, Shizuoka 431-31. Pharmacogenetics 1995;5:Spec Iss:S145-8.

Msp I polymorphism and exon 7 Ile-Val polymorphism of CYP 1A 1, and RsaI polymorphism of CYP2El were studied in lung cancer patients and controls in Rio de Janeiro, Brazil. Of the three polymorphisms studied, only the exon 7 polymorphism of CYPlAI (Val-containing genotypes) had a distribution which was statistically significant in the patients and controls. The contribution of Val containing genotypes of CYPIAl exon 7 was greater in the subpopulation of squamous cell carcinoma patients with a lower life-time smoking consumption (OR, 2.92 vs 1.97). This association is consistent with the previous findings by Kawajiri et al. and the first observation of the positive association of this locus with lung cancer in a Western population (Kawajiri K, Nakachi K, Imai K, Yoshii A, Shimada N, Watanabe J. FEBS Let 1990; 263, 131-133). Furthermore, together with the lack of association of Msp I polymorphism in the non-coding region of CYPIAI, the locus truly responsible for lung cancer risk among pleural polymorphisms of CYPlAl appeared to be exon 7 Ile-Val polymorphism. In the future, investigations of multiple markers in different ethnic populations may reveal cancer risk markers common to all mankind.

Sigma receptors are expressed in human non-small cell lung carcinoma John CS, Bowen WD. Karma VM, M&fee JG, Moody TW. Radiology Research. George Washington Univ. Med. Centeer, 2300 I St N.U!, Washington, DC 20037. Life Sci 1995;56:2385-92.

N-(2-piperidinoethyl)4-iodobenzamide), IPAB, was used to characterize sigma receptors in non-small cell lung cancer (NSCLC) cell lines. ‘-IPAB bound with high affinity to large cell carcinoma (NCI- H 1299), adenocarcinoma (NCI-H838), and lung carcinoid (NCI-H727) cell lines. Specific IPAB binding was inhibited with high affinity by