Takeshi Hirayama

Use of nitrite and hypochlorite treatments in determination of the contributions of IQ-type and non-IQ-type heterocyclic amines to the mutagenicities in crude pyrolyzed materials

The mutagenic heterocyclic amines Glu-P-2, MeA alpha C and Phe-P-1, which possess a 2-aminopyridine structure in their molecule (non-IQ-type mutagens), were found to be inactivated by nitrite treatment under acidic conditions, as observed previously with Trp-P-1, Trp-P-2, Glu-P-1 and A alpha C. In contrast, MeIQx, 4,8- and 7,8-DiMeIQx, which were originally isolated from fried beef or heated model mixtures of creatinine, amino acids and glucose, and which have a 2-aminoimidazole moiety in their molecules (IQ-type mutagens), were very resistant to nitrite treatment like IQ and MeIQ. Both types of mutagenic heterocyclic amines were completely inactivated by treatment with hypochlorite. This differential inactivation of mutagenic heterocyclic amines by nitrite and hypochlorite was used in determination of the contributions of IQ-type and non-IQ-type mutagens to the total mutagenicities of various pyrolyzed materials. The percentage contributions of IQ-type mutagens to the mutagenicities of broiled sardine, fried beef, broiled horse mackerel, cigarette smoke condensate and albumin tar were 88, 75, 48, 6 and 4, respectively.

Inactivation of mutagens from pyrolysates of tryptophan and glutamic acid by nitrite in acidic solution

The mutagenic aromatic amines Trp-P-1, Trp-P-2 and Glu-P-1, isolated frm pyrolysates of tryptophan and glutamic acid, at the concentration of 0.025 mM were treated with 0.05 mM nitrite at various pH values at 37 degrees C. The resulting reaction mixtures were tested for mutagenicity towards Salmonella typhimurium TA98 and TA100. When treated with nitrite at this physiologically realistic concentration, these mutagenic aromatic amines were readily converted to extremely weak or non-mutagenic deaminated compounds. These deaminated products were identified as the corresponding hydroxy compounds by mass and proton magnetic resonance spectroscopies. Comparative kinetic studies were made on the disappearance of the mutagenic aromatic amines. The half-life (t1/2 of Glu-P-1 on treatment with nitrite at pH 1.6 was less than 5 min, and those of Trp-P-1 and Trp-P-2 were 95 and 105 min, resp.

Increase in the levels of N-nitrosoproline, N-nitrosothioproline and N-nitroso-2-methylthioproline in human urine by cigarette smoking

The effects of cigarette smoking on the urinary excretions of N-nitrosoproline (NPRO) and the sulfur-containing N-nitrosamino acids, N-nitrosothioproline (NTPRO) and N-nitroso-2-methylthioproline (NMTPRO), in a male volunteer were examined. This subject smoked for 20 non-consecutive days and did not smoke for another 20 non-consecutive days during a 4-month-period, and 24-h urine samples were collected. On the days of urine collection, he was given a fixed diet. On the smoking days, the urinary levels of NPRO, NTPRO and NMTPRO increased significantly from 1.1 +/- 0.5 (mean +/- S.D.) micrograms/day to 1.8 +/- 0.9 (P less than 0.01), from 3.9 +/- 1.1 to 8.7 +/- 4.6 micrograms/day (P less than 0.001), and from 5.6 +/- 1.9 to 8.5 +/- 4.1 micrograms/day (P less than 0.01), respectively. Thus, the total amount of these 3 N-nitrosamino acids in the urine also increased significantly by smoking from 10.6 +/- 2.8 to 19.0 +/- 6.5 micrograms/day (P less than 0.001). These results indicated that NOx in cigarette smoke can contribute to in vivo formation of N-nitroso compounds.

Nitrite converts 2-amino-α-carboline, an indirect mutagen, into 2-hydroxy-α-carboline, a non-mutagen and 2-hydroxy-3-nitroso-α-carboline, a direct mutagen

Abstract 2-Amino-α-carboline [26148-68-5] which was isolated from a pyrolysate of soybean globulin and which was mutagenic to Salmonella typhimurium in the presence of a rat-liver microsomal fraction (S9 mix), was converted into non-mutagenic 2-hydroxy-α-carboline by treatment with nitrite in acidic conditions. However, on prolonged treatment with nitride and acid, 2-hydroxy-α-carboline was further converted into a new mutagen which did not require S9 mix for exhibition of the mutagenicity. This direct-acting mutagen was found to be 2-hydroxy-3-nitroso-α-carboline by mass and proton magnetic resonance spectroscopies.

Changes in the sebaceous gland in patients with male pattern hair loss (androgenic alopecia).

The sebaceous gland and the follicular bulge region have important role in biology of the hair. They initiate destruction of the hair follicle both in human and animal models in certain conditions. The morphometric feature of the sebaceous gland is not well understood so as the distribution of the bulge stem cells in pathological conditions of male pattern hair loss or androgenic alopecia (AGA).