TABLE III.

Mutations in the cII Gene of Spleen From AA-Treated and Control Male Big Blue® Rats

				Number of mutations (independent)
					AA (mg/kg body weight)
Positiona	Mutationb	Amino acid change	Sequence context 5′ → 3′c	Control	0.1	1.0	10.0
−18	C → G	N/A	tatCTAagg				1
−13	G → A	N/A	ctaAGGaaa				1
−1	T → C	N/A	ttaCATatg				1
1	A → G	Met → Val	catATGgtt			1	4 (2)
	A → T	Met → Leu	catATGgtt			1
2	T → A	Met → Lys	catATGgtt			1 d	1
	T → C	Met → Thr	catATGgtt				2 d
3	G → A	Met → Ile	catATGgtt		1	1
	G → C	Met → Ile	catATGgtt				1
	G → T	Met → Ile	catATGgtt		2(1)		1
4	G → C	Val → Leu	atgGTTcgt			1
14	A → T	Asn → Ile	gcaAACaaa				1
15	C → A	Asn → Lys	gcaAACaaa	1
16	A → T	Lys → Stop	aacAAAcgc			2
19	C → T	Arg → Cys	aaaCGCaac	1
24	C → G	Asn → Lys	cgcAACgag				1
25	G → A	Glu → Lys	aacGAGgct	3			2
	G → T	Glu → Stop	aacGAGgct	1	1
26	A → G	Glu → Gly	aacGAGgct				1
	A → T	Glu → Val	aacGAGgct				3
28	G → A	Ala → Thr	gagGCTcta		1
	G → C	Ala → Pro	gagGCTcta				1
31	C → G	Leu → Val	gctCTAcga			1	1
32	T → C	Leu → Pro	gctCTAcga				1
34	C → G	Arg → Gly	ctaCGAatc				1
	C → T	Arg → Stop	ctaCGAatc	4	1	1
35	G → A	Arg → Gln	ctaCGAatc	1		1	1
	G → C	Arg → Pro	ctaCGAatc				1
	G → T	Arg → Leu	ctaCGAatc				1
38	T → A	Ile → Asn	cgaATCgag				1
39	C → G	Ile → Met	cgaATCgag			1
40	G → A	Glu → Lys	atcGAGagt		1		2
43	A → G	Ser → Gly	gagAGTgcg			1
47	C → G	Ala → Gly	agtGCGttg				1
	−C	Frameshift	agtGCGttg				1
49	T → A	Leu → Met	gcgTTGctt				1
50	T → C	Leu → Ser	gcgTTGctt				1
51	G → T	Leu → Phe	gcgTTGctt			1
53	T → C	Leu → Pro	ttgCTTaac				1
55	A → C	Asn → His	cttAACaaa				1
58	A → T	Lys → Stop	aacAAAatc				1
	A → G	Lys → Glu	aacAAAatc				1
60	+AATCGC	Frameshift	aacAAAatc			1
60	A → T	Lys → Lys	aacAAAatc		1
63	C → G	Ile → Met	gcaATCgca				1
64	G → A	Ala → Thr	atcGCAatg		1		4
68–69	−TG	Frameshift	gcaATGctt			1
71	T → C	Leu → Pro	atgCTTgga		1		1
73	G → A	Gly → Arg	cttGGAact	1			1
74	G → T	Gly → Val	cttGGAact	1
77	C → A	Thr → Asn	ggaACTgag			1
82	A → G	Lys → Glu	gagAAGaca				1
86	C → G	Thr → Arg	aagACAgcg				2
89	C → A	Ala → Glu	acaGCGgaa				2(1)
	C → T	Ala → Val	acaGCGgaa	1	2		1
90–91	−G	Frameshift	acaGCGGAAgct				1
94	G → A	Ala → Thr	gaaGCTgtg				1
	G → T	Ala → Ser	gaaGCTgtg			1
99–101	−G	Frameshift	gctGTGGGCgtt				1
100	G → A	Gly → Ser	gtgGGCgtt				1
	G → T	Gly → Cys	gtgGGCgtt			1
101	G → T	Gly → Val	gtgGGCgtt				1
103	G → A	Val → Ile	ggcGTTgat	3 (2)	3 (2)	5 (2)	3
	G → C	Val → Leu	ggcGTTgat	1		1
	G → T	Val → Phe	ggcGTTgat	1
104	T → A	Val → Asp	ggcGTTgat			1	1
108	T → A	Asp → Glu	gttGATaag				1
109	A → G	Lys → Glu	gatAAGtcg				1
	A → T	Lys → Stop	gatAAGtcg			1
110	A → T	Lys → Met	gatAAGtcg				2
111	G → T	Lys → Asn	gatAAGtcg				1
113	C → T	Ser → Leu	aagTCGcag	1		1	1
115	C → T	Gln → Stop	tcgCAGatc				1
116	A → T	Gln → Leu	tcgCAGatc				1
118	A → T	Ile → Phe	cagATCagc	1
119	T → A	Ile → Asn	cagATCagc			1
120	C → G	Ile → Met	cagATCagc		1
124	A → T	Arg → Trp	agcAGGtgg				2
125	G → T	Arg → Met	agcAGGtgg			1
127	T → A	Trp → Arg	aggTGGaag				3
129–132	+A	Frameshift	aggTGGAAGagg				1
129	G → A	Trp → Stop	aggTGGaag				1
	G → C	Trp → cys	aggTGGaag			1
130	A → T	Lys → Stop	tggAAGagg				1 d
135	G → C	Arg → Ser	aagAGGgac			1
139	T → A	Trp → Arg	gacTGGatt				4 (3)
141	G → T	Trp → Cys	gacTGGatt	1			1
145	C → A	Pro → Thr	attCCAaag				1
146	C → A	Pro → Gln	attCCAaag	1
150	G → T	Lys → Asn	ccaAAGttc	1	1		1
158	T → C	Met → Thr	tcaATGctg			1
159	G → A	Met → Ile	tcaATGctg				1
161	T → A	Leu → Gln	atgCTGctt				2
	T → C	Leu → Pro	atgCTGctt				1
164	T → A	Leu → His	ctgCTTgct				2
167	C → G	Ala → Gly	cttGCTgtt	1
172	C → A	Leu → Ile	gttCTTgaa				1
	C → T	Leu → Phe	gttCTTgaa				1
	−C	Frameshift	gttCTTgaa				1
175	G → C	Glu → Gln	cttGAAtgg				1
	G → T	Glu → Stop	cttGAAtgg				1
176	A → T	Glu → Val	cttGAAtgg			1	2
178/185	+G	Frameshift	gaaTGGGGGGTCgtt	4 (2)	4 (3)	5 (2)	5 (4)
178	T → A	Trp → Arg	gaaTGGggg				3
179	G → A	Trp → Stop	gaaTGGggg			1	3
179–184	−G	Frameshift	gaaTGGGGGGTCgtt	1	2 (1)	3	6 (3)
181	G → T	Gly → Trp	tggGGGgtc				1
182	G → T	Gly → Val	tggGGGgtc				3
185	T → A	Val → Asp	gggGTCgtt			1	2
	T → C	Val → Ala	gggGTCgtt				1
	T → G	Val → Gly	gggGTCgtt	1			1
190	G → C	Asp → Gln	gttGACgac	1
	G → T	Asp → Tyr	gttGACgac				1
190–192	−GAC	Frameshift	gttGACgac	1
191	A → G	Asp → Gly	gttGACgac				1
191–192	AC → TT	Asp → Val	gttGACgac				1
193	G → A	Asp → Asn	gacGACgac	1	1		5 (3)
	G → C	Asp → His	gacGACgac				4(1)
	G → T	Asp → Tyr	gacGACgac			1	2
193–194	GA → TT	Asp → Tyr	gacGACgac	1
194	A → T	Asp → Val	gacGACgac				1
196	G → A	Asp → Asn	gacGACatg	4 (3)	2	1	3
	G → C	Asp → His	gacGACatg				2
	G → T	Asp → Tyr	gacGACatg	1			1
199	A → G	Met → Val	gacATGgct				4 (3)
200	T → A	Met → Lys	gacATGgct				1
	T → C	Met → Thr	gacATGgct				1
201–202	−G	Frameshift	gacATGGCTcga			1
202	G → C	Ala → Pro	atgGCTcga				1
206	G → A	Arg → Gln	gctCGAttg	2 (1)		1
	G → C	Arg → Pro	gctCGAttg			1	1
208	T → A	Leu → Met	cgaTTGgcg				2(1)
209	T → A	Leu → Stop	cgaTTGgcg				2
210	G → T	Leu → Phe	cgaTTGgcg				3
211	G → C	Ala → Pro	ttgGCGcga	1
212	C → A	Ala → Glu	ttgGCGcga			2
	C → G	Ala → Gly	ttgGCGcga				1
	C → T	Ala → Val	ttgGCGcga	2	7 (2)	3	6 (5)
214	C → A	Arg → Arg	gcgCGAcaa				1
	C → T	Arg → Stop	gcgCGAcaa	3	3 (2)	3 (2)	10(5)
215	G → T	Arg → Leu	gcgCGAcaa				1
217	C → T	Gln → Stop	cgaCAAgtt				1
218	A → T	Gln → Leu	cgaCAAgtt				3
220	G → A	Val → Ile	caaGTTgct		1
	G → T	Val → Phe	caaGTTgct	1
224	C → A	Ala → Asp	gttGCTgcg			1
226	G → C	Ala → Pro	gctGCGatt		1
228	−G	Frameshift	gctGCGatt			1	3 (1)
230	T → A	Ile → Asn	gcgATTctc				1
232	C → T	Leu → Phe	attCTCacc				1
233	T → A	Leu → His	attCTCacc				1
	T → C	Leu → Pro	attCTCacc			1
240	−T	Frameshift	accAATaaa				1
241	A → T	Lys → Stop	aatAAAaaa				1
241–246	−A	Frameshift	aatAAAAAAcgc				1
253	−G	Frameshift	ccgGCGgca				1
274	C → A	Gln → Lys	gaaCAAatc				1
	C → G	Gln → Glu	gaaCAAatc		1
275	A → T	Gln → Leu	gaaCAAatc			1
276	A → T	Gln → His	gaaCAAatc				1
287	A → T	Glu → Val	atgGAGttc	1
292	T → A	Stop → Arg	ttcTGAggt		1
	T → C	Stop → Arg	ttcTGAggt	1
293	G → C	Stop → Ser	ttcTGAggt			1
	G → T	Stop → Leu	ttcTGAggt	1
294	A → G	Stop → Trp	ttcTGAggt				1
	A → T	Stop → Cys	ttcTGAggt		1		3
Total				52 (47)	41 (31)	61 (54)	196 (173)

Abbreviations: −, deletion; +, insertion

^aPosition 1 is the first base of the start codon in the cII coding sequence.

^bPresented in term of sequence change on nontranscribed DNA strand.

^cUppercase indicates target codon and target bases are underlined.

^dComplex mutation.