adduct. The purpose of these studlcs wa\ to identify and characterize the activated oncogcncs prcsem m tumors induced by NDMA and NNK. Followmg transfectlon of high molecular weight DNA onto NIH/3T3 mouse flbroblasts, transforming genes were dctcctcd m 90% of both NNK- (loaf 1l)and NDMA- (9of 10) mduccd lung tumors. Incontrast, transl’ormation of NIH/3T3 Ilbroblasts w’as observed only m 40% (2 of 5) and 13% (I of 8) of the hver tumors from NNK- and NDMA-treated mice, rcspccrively. Southern blot analysis Indicated that the transCorn- mg gcnc prcscnt in all lung tumors was an activated K-ras oncogene. Both rcarrangcd bands and ampliflcd signals wcrc dctccted in the uansfectants. The one transformant from the NDMA-induced liver tumor contained an actlvatcd K-ras gcnc. In contrast. the two hver transformants from NNK-induced tumors did not contain an activated ras or raf gene. Hybridization with oligonuclcotldc probes that were ccntercd around cithcr codon 12 or 61 of the K-ras gene were utilized to localix the mutations. Activation of this gene appeared to occur largely via a mutation m codon 12 (15 ot” 20 transformants) and was obscrvcd with a similar frcqucncy m pulmonary tumors induced by clthcr compound. The remaining mutations wcrc found in codon 61. The speLlTIc mutaoon wlthin thcsc Tao codons was dctcrmmed by amphfymg rhc cxon conrammg the bavz change, followed by direct scqucncmg. Wuh one exception the mutation obscrvcd in codon 12 was

a GC to AT transition (GGT to GAT). One transformantcontained a GC to TA transvcrslon. The activating mutation detected in codon 61 was always an AT to GC transitIon of the middle A (CAA to CGA). The GC to AT mutation obscrvcd in codon 12 is consistent with the formation of the 06-mcthylguanineadduct. Slmilarconcentrations (23 to 32 pmol/ pmol dcoxyguanosme) of this promutagemc adduct were detected in lungsduringtreatment witheitherNNKor NDMA. Acomparisonofthe mutation patterns obscrvedpreviously m spontaneous lung tumors from A/J mice wjith those dctectcd m NNK- and NDMA-induced tumors mdicatcs that chemically mediated activation of the K-ras gene occurs via a dlrcct genotoxic mechanism involving the formation of the 0’. methylguaninc adduct. Almost 100% of the mutations in codon 12 were GC to AT transltions in chemically Induced tumors, while this base change H8a.s prcscnt in only 50% of the sponuncous tumors with codon 12 mutations. The fact that the mutation prol~les observed foractivation of the K-ras gene by NNK and NDMA wcrc identical indicates that DNA mcthylarion and notpyridyloxobutylation IS most likely the major pathway involved m the InductIon ol- pulmonar) ncoplasia by NNK.

Further follow-up and adjustment for smoking in a study of lung cancer and acid mists Stccnland K, Beaumont J. Naluxzul Insuu~e for Orcupa~mml Safely and ffealth. Cincinnnrl, Off 45226 Am J lnd Mcd 1989;16:347-54.

Follou-up ofacohonof 1.165 stcclworkcrs exposed to acid mists has been extended from 1981 IO early 1986 for most cohort members, and mformation on smoking has also been collected. WC obtained an SMR forlungcancer(unadjustcdforsmoking)of 1.56 (95% Cl 1.12-2.1 I,41 observed). For those with 20 years or more bincc first cxposurc, the SMR was 1.72 (1 .?l-2.39). Howcvcr, no trend was found with duration of exposure. To adjust for smoking, WC used an mdircct adjustment as suggested by Axclson to account for the fact that the exposed cohort smoked slightly more than the U.S. rcfcrcnt population. The SMR for the whole cohortdroppcd to 1.36(0.97-l .84), wjhdc forthosc with more than 20 years since flrstcxposurc, the SMR was 1 SO (1 X15-2.07). These results indxate that an excchh ml, lor lung cancer pcrslbta after control for confounding by rmoklng.

Estimating Rn-induced lung cancer in the United States Lubin JH, Boice JD Jr. B~osfalisrlcsEranrh, ~ppidemlofogyandBiosra- lislics Program, National Cancer fn.rtrtu!e, BelheAda. MD 20892. Health Phys 1989:57:417-27.

The proportion of lung cancer deaths attributable to Rn among resldcnb of singlc-family homes in the U.S. (approximately 70% of the

housing stock) is estlmatcd using the log-normal distribution of Rn concentrations proposed by Nero et al. (1986) and the risk model developed by the National Academy of Scvxccs’ BEIR IV Committee. The risk model, together with the cxposurc distribution, prcdicb that approximately 14% of lung cancer deaths among such residents (about 13,300 deaths per year, or 10% of all U.S. lung cancer deaths) may be due to indoor Rn exposure. The 95% confidence interval is 7%-25%, or approximately 6600 to 24,000 lung cancer deaths. These estimated attributable risks due to Rn are similar for males and females and for smokers and nonsmokers, but higher basclinc risks for lung cancer result in much larger absolute numbers of Rn-attributable cancers among males (approximately 9ooO) and among smokers (approxi- mately 11,000). Because of the apparent skewness of the exposure distribution,mostofthecontribuuonto theattributablcrisksariscsfrom exposure rates below 148 Bq m 3 (4 pCi L-l), i.e., below the EPA ‘action lcvcl.’ As a result, ifall exposure rates that exceed I48 Bq m 3 (approxi- mately 8% of homes) were elimmatcd, the models predict that the total annual lung cancer burden in the U.S. would drop by 4-5%, or by about 3800 lung cancers deaths, in contrast to a maximum reduction of 14% if all indoor Rn exposure above the 1st pcrcenule were eliminated.

Mineral fiber concentration in lung tissue of mesothelioma patients in Finland Tuomi T, Segerberg-Konttincn M, Tammilchto L, Tossavainen A, VanhalaE. Institute of Occupational ffealth. SF-00250flelsinki. Am J Ind Med 1989;16:247-54.

The mineral fibers m lung tissue samples of 19 mesothelioma patients and 15 randomly selected autopsy cases were analyzed using low-tcmpcrature ashing, scanning electron microscopy (SEM) and x- ray microanalysls. The fiber concentration ranged from 0.5 to 370 million fibers per gram of dry tissue m the mcsothclioma group and from ~0.1 to 3.2 million fibers per gram of dry tissue in the autopsy group. In 80% of the mesothelioma pailcots and m 20% of the autopsy cases, the fiber concentration cxcccdcd 1 million fibers pergram of dry 11ssuc. Amphibole asbestos fibers prcdommated in both groups, and only a few chrysotilc fibers were found. In the lungs of su mcsotheli- oma patients, anthophyllitc was the main fiber type. The overall analytical precision ol’ sampled preparation and fiber counting with SEM wsa 22%.

Relation between asbestosis and bronchial cancer in amphibole asbestos miners Sluis-Crcmcr GK, Bezuidcnhout BN. Epidemiology Research Unik MedicalBurruuofOccupaiionul Di.reare,.fohanneshurg2000. BrJ Ind hlcd 1989;46:537-40.

In a necropsy series of 339 amphlbolc asbestos miners heavy smok- ing, age, and the presence of asbestosis w’erc significantly associated with the prcscncc of bronchial cancer. Of the 35 cases of bronchial cancer, 24 were associated with asbcstosis. Eleven cases of bronchial cancer occurred m men withoutasbcstosis; all were smokers. Standard- lvcd proportional mortality rates indlcatcd no excess of bronchial cancer m 302 exposed men without asbc>tous whereas these rates were progrcsslvcly raised m men with slight or modcratc/scvcre asbcstosis. Or the four cxposurc variables muoduccd xparatcly into a logistic rcgrcsslon model, ‘years of cxposurc’ made a small but significant contribution; ‘residence tlmc’ marginally falled to achieve a 5% lcvcl of significance. Two other cxposurc variables tcsrcd including cumula- tive flbrc cxpohurc (fibrc years) made no signlficantconuibu~on. In the absence of asbcstosis at nccorpsy a hronchlal cancer in a man exposed IO asbcytos 1, unlikely to bc due to a\bcstos.

Lung cancer in chromate workers: High-risk group for multiple lung cancer Uyama T, Monden Y, Tsuyuguchi M, Harada K, Kimura S, Taniki T. Second Deparmenr of Sur,qery, School of Medxine, The Universiry of