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HT®012114$ CTR 1Q1B EXPOSURE OF BC3F1/CUM MICE TO 2R1 AND 3A1 CIGARETTE SMOKE FOR ONE YEAR I I

NT®0121150 1 TABLE 12 SPECIFIC ACTIVITY OF 14C-DOTRIACONTANE (DTC) IN CAMBRIDGE FILTER PADS (dpm-14C-DTC/mg TPM) Smoke Regimen mg TPM/pad dpm/pad dpm/ug TPM 15 sec. smoke/45 sec. air B puffs, 8 cigarettes 1.04 54,000 51.92 20 sec. sm-oke/40 sec. air 9 puffs, 10 cigarettes 1.69 86,200 51.01 30 sec. sm-oke/30 sec, air 2.842 142,200 50.04 9 puffs, 15 cigarettes

HT1012115- TABLE 13 ESTIMATED TOTAL PARTICULATE MATTER DEPOSITED IN PULMONARY TISSUES OF BCJF1/CUM FEMALE MICE FOLLOWING EXPOSURE TO WHOLE SMOKE FROM 2R1 REFERENCE CtGARETTESB Smoke Regimen Lungb Tracheab Larynxb 15 sec. smoke/45 sec. air 8 puffs 24.7 2.4 2.5 20 sec. smoke/40 sec. air 9 puffs 27.0 2.6 2.5 30 sec. smoke/30 sec. air 9 puffs 89.3 2.9 3.2 aTen (10) mice were analyzed at each regimen. bData are given in terms of pg TPM deposited per cigarette run. I

~,. - „ t_ --------^ _ HT10121152 TABLE 14 PULMONARY ARYL HYDROCARBON HYDROXYLASE (A8H) ACTIVITY IN BC3F1/CUM FEMALE MICE EXPOSED TO 3A1 OR 2R1 CIGARETTE SMOKE AFTER USING THE CONTINUOUS EXPOSURE REGIMEN FOR 3, 6, AND 9 MONTHSa AHH Unitsb Length of Smoke-Exposed _ Exposure (Months) 3A1 Cigarettes 2R1 Cigarettes Sham-Exposed 3 146 (0.16)c 142 (0,17) 34 (0.38) 6 228 (0.15) 226 (0.15) 42 (0.24) 9 205 (0.20) 234 (0.33) 36 (0.36) aExposure conditions were 10% 3A1 or 2R1 cigarette smoke, 17 "runs", 8 puffs/cigarette. bData are from animals sacrificed E hours after smoke exposure with AHH units in picomoles benzo(a)pyrene hydroxlrlated/mg m,icrosomal protein at 37oC. cCoefficient of variation. I

HT10121155 I TABLE 15 PULMONARY ORNITHINE OECARBOXYLASE (ODC) ACTIVITY IN BC3F1/CUM FEMALE MICE EXPOSED TO 3A1 AND 2R1 CIGARETTE SMOKE USING THE "CONTINUOUS" REGIMEN FOR 3 MONTHSa ODC Unitsb Smoke-Exposed Time After Exposure (Hoursl 3A1 Cigarettes 2R1 Cigarettes Sham Exposed 3 15.4(,.10)c 13.9(.47) 8,0(.38) 6 14.6(,.19) 16.8(.35) 9.2(.18) 9 7.0(,11) 6.9(.10) 4.5(.20) aExposure conditions were 10% 3A1 or 2R1 cigarette smoke, continuous regimen (17 "runs", 8 puffs/ cigarette). bODC-p moles C02/mg prqtein/20 minutes at 370C. cCoefficient of variation.

N10012115it TABLE 16 PULMONARY ORNITHINE DECARBOXYLASE (ODC) ACTIVITY IN SC3F1/CIIM FEMALE MICE EXPOSED TO 3A1 OR 2R1 CIGARETTE SMOKE USING THE "CONTINUOUS" REGIMEN FOR 6 MONTHSa ODC Unitsb Smoke-Exposed Time after Exposure 3A1 2R1 Sham Shelf To Last Cigarette Cigarettes Cigarettes Control Control 3 Hours 23.7(0.30)c 24.9(0.22) 12.8(0.24) 16.8(0.12) 6 Hours 13.3(0.14) 16.1(0.18) 14.1(0.21) 8 Hours 14.9(0.35) 17.1(0.25) 12.7(0.13) aExposure conditions were 10% 3A1 or 2R1 cigarette smoke, continuous regimen 17 "runs", 8 puff/cigarette. bODC-picomoles C02 liberated per sng protein per 20 minutes at 37°C. cMean and coefficient of variation from 5 micer per time point.

TABLE 19 AUTORADIOGRAPHIC ANAL'1SIS OF LABELLING INDEX IN THE TRACHEA OF BC3F1/CUM FEMALE MICE EXPOSED TO 3A1 AND 2R1 CIGARETTE SMOKE FOR 3 MONTHS Exposure Condition Mousef ?.abelled Cells Total Cells Counted Fraction Labelled Cells Average % Labelled Cell Per Exposure Group 3A1 1 20 3147 0.0064 0.68 2 33 3470 0.0095 3 23 2874 0.0080 4 11 3385 0.0033 Mean: 22+9 3219+268 0.0068+0.0027 2R1 1 47 3304 0.0142 1.62 2 89 2961 0.0301 3 !2 2800 0.0150 4 17 3138 0.0054 Mean: 49+30 3051+218 0. 0162+0. a 103 Sham 1 10 2828 0.0035 0.37 2 15 2341 0.0064 3 5 2601 0.0019 4 8 2728 0.0029 Means 10+4 2625+211 0.0037+0.0019 Shelf 1 21 2633 0.0080 0.97 2 32 2811 0.0114 27+8 2722+126 0.0097+0.0024

i TABLE 17 ~~ 1 , AUTORADIOGRAPHIC ANALYSIS OF LABELLING INDEX INDUCED IN THE LUNG OF BC3F1/CUM FEMALE MICE EXPOSED TO 3A1 AND 2:t1 CIGARETTE SMOKE FOR 3 MONTHSa ~ Fraction Average e ~ Exposure Labelled Total Cells Labelled Labelled Cells 4~ Condition Mouse4 Cells Counted Cells Per Ex osure Group ~ i 3A1 1 30 4762 0.0063 0.880 2 44 43134 0.0100 3 36 4282 0.0084 4 42 3980 0.0106 Mean: 38+6 4352+323 0.0088+0.0019 2R1 1 28 4626 0.0061 0.620 2 30 4797 0.0063 3 29 4569 0.0063 4 33 5360 0.0062 Mean: 30+2 4838+361 0.0062+0.0001 Sham 1 3 5449 0.0006 0.045 2 2 6328 0.0003 3 2 4587 0.0004 4 3 6189 0.0005 Mean: 2.5+0.6 3638+800 0.00045+0.0001 Shel£ 1 3 4855 0.0006 0.045 2 2 5846 0.0003 Mean; 2.5+0.7 5351+701 0.00045+0.0002 ~ - ~6 ~ aExposure conditions were 10% 3A1 or 2R1 cigarette smoke using the continuous regimen of ~ 17 "runs", S puffs/cigarette. ~, ~ ~ cJ" c." f

r TABLE 20 - !f( I AUTORADIOGRAPHIC ANALYSIS OF LABELLING INDEX f 1 IN THE URINARY BLADDER OF BC3F1/CUM FEMALE MICE EXPOSED TO 3A1 AND 2R1 CIGARETTE SMOKE FOR 3 MONTHS i l Exposure Labelled Total Cells Fraction of Average % Labelled Cells Conditinn Mouse$ Cells Counted Labelled Cells Per Exposure Grou 3A1 1 1 1922 0.00052 0.067 2 0 1250 0 3 6 2773 0.002.6 4 0 2001 0 ~ 2R1 1 2 1614 0.00124 0.2i7 2 3 1089 0.00275 3 5 1491 0.00335 4 3 2276 0.00132 Sham 1 5 2824 0.00177 0.193 2 1 2294 0.00044 3 4 1742 0.00230 4 2 622 0.00322 Shelf 1 1 1166 0.00086 0.090 2 3 3163 0.00095 , 1~3 ~ ~ Cs~ OD

! TABLE 18 ANALYSIS OF THE DISTRIBUTION OF GRAINS OVER NUCLEI OF LUNG CELLS IN SC3Fl/CUM FEMALE MICE EXPOSED TO 3A1 AND 2R1 CIGARETTE SMOKE FOR 3 MONTHS Exposure Cogdition Mouse4 Labelled Cells Counted Total Cells with Cells Counteda <30 Grains % Total Cells with <30 Grains Cells'with >30 Grains % Total Cells with >30 Grains 3A1 1 150 23,810 99 0.42 51 0.21 2 150 14,945 101 0.68 49 0.33 3 150 17,846 94 0.53 56 0.31 4 150 14,214 99 0.70 51 0.36 Mean: 150 17,704 98 0.58 52 0.30 (+ 4,363) (+ 3) (+0.13) (+ 3) (+0.07) 2R1 1 159 24,782 106 0.42 44 0.18 2 150 23,985 103 0.43 47 0.20 3 150 23,633 105 0.44 45 0.19 4 150 24,364 122 0.50 28 0.11 Mean: 150 24,191 109 0.45 41 0.17 (+ 494) (+ 9) (+0.04) (+ 9) (+0.04) Sham 1 150 272,450 59 0.022 91 0.033 2 150 474,600 47 0.010 103 0.022 3 150 344,025 57 0.017 93 0.027 ~ 4 150 309,450 63 0.020 87 0.028 Mean: 150 350,131 57 0.017 94 0.028 C:) (+ 87 976) (+ 7) (+0.005) (+ 7) N (+0.005) , ~ Shelf 1 150 242,750 66 0.027 84 0.035 ,~ 2 143 417,909 72 0.017 71 0.017 Lrl Mean: 147 330,370 69 0.022 78 0.026 _ (+12_,913) (± 4) (+0.007) (+ 9) (+0.013) aThese numbers were calculated on a pro rate basis from data presented in Table 17. i